PEMERIKSAAN PATOLOGI ANATOMI

PADA PENYAKIT SISTEM

PERNAPASAN (PATOLOGI TUMOR
DAN TUMOR LIKE LESSION)

Dr. YENITA, M. Biomed, SpPA

1
TRAKTUS RESPIRATORIUS

■ ATAS: hidung, sinus nasal, faring, laring

Kelainan: kongenital, radang, tumor
■ BAWAH: paru
Kelainan: kongenital, radang, tumor

2
Tumor Traktus Respiratorius
Atas
■ Jinak
- Epitel: papilloma
- Jar. Penyambung: hemangioma, angiofibroma
■ Ganas
- terutama: SCC, sering di laring
- Nasopharyngeal Carcinoma (NPC)
- Adeno ca

3
Nasal polyps

■ Chronic infective inflammation, chronic

allergic inflammation
■ Makr: lesi polipoid, mengkilat
■ Mikr: massa tda stroma edematous polipoid
yang diinfiltrasi oleh sel-sel radang,
khususnya sel plasma, limfosit; eosinofil
(bila etionya alergi), adanya kelenjar-
kelenjar mukus

4
5
6
7
8
Exophytic papilloma
(Schneiderian papilloma,
exophytic type)
■ A papilloma derived from the Schneiderian
membrane composed of papillary fronds
with delicate fibrovascular cores covered by
multiple layers of epithelial cells.

9
Exophytic papilloma.
A. Papillary growth arising from the nasal septum.
B. Higher magnification showing the hyperplastic non-keratinizing squamous
epithelium with scattered clear (mucous) cells.
C.Small neutrophilic abscess can be seen within the epithelium on occasion.
D. Koilocytic change (nuclear chromatin condensation, perinuclear halo and
accentuation of the cell border) seen in exophytic papillomas
10
Singer’s nodes pada pita suara
■ Penggunaan suara yg berlebihan
■ Guru, penyanyi
■ Merubah karakter suara
■ Vocal cord nodule/laryngeal polyps
■ Nodul tunggal, diameter bbrp mm
■ Mikr: stroma miksoid edematous, permukaan
dilapisi epitel berlapis gepeng, amyloid-like
material pd stroma

11
Diagrammatic comparison of a benign papilloma and an
exophytic carcinoma of the larynx to highlight their quite
different appearances.

12
13
14
Karsinoma laring

■ 2% dari keseluruhan kanker

■ ♂ : ♀ = 7 :1
■ > 40 th
■ rokok, alkohol, asbestos
■ 95% jenis SCC

15
A. Karsinoma laring. Lesi yang besar, ulserasi, fungating melibatkan
pita suara dan sinus piriformis. B, Histologi: SCC laring.
16
Nasopharyngeal angiofibroma

■ A benign, highly cellular and richly

vascularized mesenchymal neoplasm that
involves the nasopharynx in males.
■ ≈Juvenile nasopharyngeal angiofibroma;
angiofibroma; fibroangioma; fibroma
■ Boys and adolescent to young men are
almost exclusively affected, with a peak in
the 2nd decade of life.

17
■ arises in the posterolateral nasal wall or the
nasopharynx
■ Nasal obstruction and/or recurrent, spontaneous
epistaxis, nasal discharge, facial deformity
(including proptosis), diplopia, exophthalmos,
sinusitis, otitis media, tinnitus,rhinolalia,
deafness, headaches,dyspnoea, and rarely,
anosmia or pain

18
■ size up to 22 cm, with a mean of about 4 cm.
■ polypoid with a rounded or multinodular
contour, with red, grey-tan cut surfaces
a vascular proliferation set in a fibrous stroma.
The vessels are mostly thin-walled, slit-like
(“staghorn”) or dilated

19
Nasopharyngeal angiofibroma. The intact respiratory epithelium overlies a
richly vascular neoplasm which has variably-sized vessels surrounded by a
cellular fibroblastic stroma with collagen.
20
NPC

21
NPC

■ Suatu karsinoma yg berasal dr mukosa nasofaring yg

secara mikroskopik memperlihatkan diferensiasi
skuamosa
■ KNF unik: - etiologi
- distribusi endemik
- etnik & daerah

risiko penyakit
insiden yang berbeda secara geografis & etnik
berhubungan dengan infeksi EBV

22
NPC

■ Global, tahun 2000: 65.000 kasus baru &

38.000 †
■ Insiden jarang di beberapa negara: Amerika
1-2 kasus/ 100.000 ♂ & 0,4 kasus/100.00
♀
■ Insiden tinggi pada kelompok etnik tertentu
■ Insiden tertinggi: Cina bagian Selatan >
50/100.000

23
24
■ Indonesia: th 2011, urutan 1 pada ♂ dan
urutan ke- 9 pada ♀.
■ Padang, th 2011, urutan ke- 7 pada ♂ dan ke-
9 pada ♀.
■ Data Lab PA FKUA, RSUP Dr. M. Djamil, RSAM
2006-2008: 45 kasus KNF di wilayah propinsi
Sumbar
■ ♂>♀
■ Semua umur, puncak umur 40-60 tahun
■ Tidak ada gejala spesifik
■ > 70% kasus: limfadenopati servikal

25
Klasifikasi NPC

■ Keratinizing Squamous Cell Carcinoma

■ Non-Keratinizing Squamous Cell Carcinoma
- Differentiated subtype
- Undifferentiated subtype
■ Basaloid Squamous Cell Carcinoma

26
Klasifikasi NPC
Keratinizing Squamous Cell Carcinoma

27
Non-Keratinizing NPC, differentiated subtype
,

28
Non-Keratinizing NPC, undifferentiated subtype

29
30
■ Faktor etiologi utama:
- infeksi EBV
- kerentanan genetik
- lingkungan

31
PARU

32
33
34
Tumor Paru
■ Benign
■ Malignant
■ 90-95%: carcinoma
■ 5%: carcinoid
■ 2-5%: mesenchym dan neoplasma lainnya
■ Kanker terbanyak dan termasuk yg paling
mematikan
■ Pada ♂ : 85-90% berhubungan dg merokok
(♀ 47%)
■ Insiden: usia 40-70 th, puncak 50-60th
35
36
37
 Etiologi dan Patogenesis

■ Akumulasi abnormalitas genetik:

Epitel bronkhus normal  neoplasma
A. Merokok
– Merokok  kanker paru
■ Jumlah rokok/hari
■ Cara merokok  inhalasi
■ Lamanya merokok
■ Terjadi perubahan histologik epitel yang melapisi trakt. respirasi
pada perokok (Pada SCC: Sq metap  sq displ  ca in situ  ca
invasive)
■ > 1200 substansi dlm asap rokok  potensial karsinogen
(polyciclic aromatic hydrocarbon (benzopyrene) inisiator; derivat
phenol  promotor; zat radio aktif lain (polonium 210, carbon 14,
potasium-40): kontaminant (arsen, nikel)
38
B. Industri
– Radiasi ionisasi dosis tinggi
– Uranium  non smoker 4x
 smoker 10 x
– Asbestos (masa laten 10-30 tahun)
 non smoker 5x
 smoker 50-90x
C. Polusi udara
– Polutant atmosfer
– Radon  dosis tinggi  tambang
 dosis rendah  indoor exposure

39
40
D. Molecular genetics
■ Paparan terhadap agen tsb  perubahan genetik
pada sel-sel paru  akumulasi  fenotip
neoplastik
■ Onkogen:
- c-MYC  small cell
- K-RAS  non small cell  late
- EGFR
- HER-2/neu
■ Gen supresor tumor
- mutasi p53  small/non small cell
- mutasi RB  small cell
- mutasi p16  non small cell
- multiple loci pada kromosom 3p  early 41
E. Predisposisi genetik
– Polimorfisme pada cytochrome P-450 gene
CYP1A1
F. Lesi prekursor
1. squamous dysplasia & ca in situ
2. atypical adenomatous hyperplasia
3. diffuse idiopathic pulmonary neuroendocrine
cell hyperplasia
42
Manifestasi Klinis

■ Batuk (80% kasus): infeksi distal sal nafas

tersumbat oleh tumor
■ Hemoptisis (70% kasus): ulserasi tumor pada
bronkhus
■ Sesak nafas (60% kasus): ekstensi lokal tumor
■ Nyeri dada (40% kasus): mengenai pleura &
dinding dada
■ Wheezing (15% kasus): penyempitan sal nafas

43
44
Klasifikasi

Penting  pengobatan
 dasar penelitian epidemiologi
dan biologi
Secara garis besar
1. Squamous cell carcinoma (25% - 40%)
2. Adenocarcinoma (25% - 40%)
3. Small cell carcinoma (20% - 25%)
4. Large cell carcinoma (10% - 15%)

45
46
■ Dalam 2 dekade terakhir insiden Adeno Ca ↑
 perubahan tipe cigaret (filter tips, kadar tar
dan nikotin ↓  perokok menghirup lebih
dalam  saluran nafas &sel-sel respirasi bag.
perifer
■ Secara Klinis:
1. Small cell ca
- sering bermetastasis
- High initial respons to chemotherapy
2. Non small cell ca
- jarang bermetastasis
- kurang respon terhadap kemoterapi 47
Morfologi

■ Sekitar hilus
■ ¾ lesi  bronkhus 1-2-3
■ Adeno ca  bronkhiolus terminalis / epitel
alveoli
■ SCC: mulai sebagai daerah displasia 
insitu  selang beberapa waktu 
penebalan mukosa daerah kecil (<1cm2)
 erosi epitel / massa tak teratur menjadi
massa intra luminal
48
Lesi prekursor SCC
49
■ SCC
Bisa menembus dinding bronkhus 
menginfiltrasi sepanjang jar. peribronkhial
 carina / mediastinum
Massa tumor: - putih abu-abu
- padat / keras
Bisa ada perdarahan/nekrosis (putih
kekuningan & lunak)
Kadang – kadang  cavitasi

50
51
■ Erosi epitel  pemeriksaan sitologi
– sputum
– broncho alveolar lavage fluid
– FNAB
■ Penyebaran tumor
- lokal
- jauh: melalui jalur limfogen / hematogen

52
53
■ Kanker paru menyebar luas ke seluruh
tubuh dalam stadium dini kecuali SCC.
■ Sering gejala metastasis merupakan
manifestasi klinis pertama.
■ Lokasi metastasis :
- Adrenal: (50%)
- Hati : ( 30-50%)
- Otak : (20%)
- Tulang : (20%)

54
SQUAMOUS CELL CARCINOMA
■ >> ♂, merokok
■ Cendrung: centrally in major bronchi
■ Histologi
– Karakteristik  Keratinisasi dan / atau
Jembatan Interseluler
– Keratinisasi: horn pearl / Individual cell
– Well, moderate, poorly differentiated
■ Mutasi gen p53, Rb,
■ CDK inhibitor P16,  tidak aktif  65% tumor
■ Overekspresi EGFR, tapi jarang mutasi  80%
■ Overeksprasi HER2/ neu  30 %
55
Squamous Cell Carcinoma

56
ADENOCARCINOMA
■ Lesi di perifer, smaller
■ >>♀, nonsmoker
■ Well diff, glandular, papillary, solid + musin sedikit
■ 80%  mengandung musin
■ Tumbuh lambat (dibanding SCC)
■ Metastasis cepat, luas
■ Daerah sikatriks
■ Dibanding SCC / small cell (98%) lebih sedikit
berhub dgn merokok
■ Mutasi K-RAS mutasi
■ Inaktivasi dan mutasi p53, RB, p16

57
VARIAN BRONCHIOLOALVEOLAR
CARCINOMA
■ Terminal daerah bronkhioloalveolar
■ 1%-9% dari kanker paru
■ Perifer  lebih sering multipel nodule, 
menyatu  menyerupai konsolidasi
pnemonia
■ mucinous / gray translucent / solid putih
abu-abu
■ Ok tumor tidak melibatkan bronkhus utama,
atelektasis dan emfisema jarang

58
■ Histologis : Cara Tumbuh “Lepidic” , butterflies sitting on
a fence (tumbuh tanpa mendestruksi struktur alveolar)
■ Subtipe non mucinous : sel epitel columnar / cuboidal,
jarang menyebar  terapi operasi
■ Subtipe mucinous  sel epitel torak tinggi dengan
musin sitoplasmik dan intra-alveolar, tumbuh sepanjang
septa alveolar, menyebar  sukar operasi
■ Adeno ca bisa berasal dari atypical adenomatous
hyperplasia  bronchioloalveolar carcinoma

59
60
Adenocarcinoma
61
Bronchioloalveolar carcinoma
62
Bronchioloalveolar carinoma, mucinous
63
SMALL CELL CARSINOMA
■ Highly malignant, high grade
■ Paling agresif dari semua kanker paru
■ Metastasis luas
■ ≠ Surgery
■ Hubungan erat merokok / 1% non
smoker
■ Bronkhus utama/perifer
■ Mutasi p53 (50%-80%) dan RB (80%-100%)
■ BCL2 ↑ (anti-apoptotic gene)
■ BAX ↓ (pro-apoptotic gene)
64
MIKROSKOPIK:
■ Sel kecil, sitoplasma sedikit, batas sel tidak tegas,
bentuk sel bulat, oval, spindle, kromatin inti
bergranul halus (salt and pepper pattern)
■ Nukleoli tidak ada / tidak banyak
■ Nuclear molding
■ Ukuran sel < 3 small resting lymphocyte
■ Gland / squamous (-)
■ Necrosis (+)
Diduga berasal dari neuroendocrin progenitor cells
(neuro endocrin marker positive, seperti:
chromogranin, synaptophysin)
65
66
67
Small-cell lung carcinoma. A, Nests and cords of round to polygonal cells with
scant cytoplasm, granular chromatin, and inconspicuous nucleoli. Note mitotic
figure in center. B, Cytologic preparation from a case of small-cell carcinoma
demonstrating "nuclear molding" of adjacent cells (arrows). This is a useful
feature in bronchioloalveolar lavage samples or fine-needle aspiration
specimens for diagnosing small-cell carcinoma. 68
 LARGE CELL CARCINOMA
■ Undifferentiated
■ Sel dg inti besar, nukleoli nyata, sitoplasma sedang

69
70
■ Combined ca
+ 10% dr semua ca paru: kombinasi 2/> dr
tipe di atas

71
72
CARCINOID TUMOR
■ 1% - 5% dr keseluruhan tumor paru
■ Usia < 40 th, ♂ ≈♀,
■ 20% - 40% pasien: nonsmoker
■ Low grade malignant epithelial neoplasm:
- typical: mitosis < 2 / mm², nekrosis (-)
- atypical: mitosis 2-10 / mm², nekrosis (+)

73
A, Bronchial carcinoid growing as a spherical, pale mass (arrow)
protruding into the lumen of the bronchus. B, Histologic appearance
of bronchial carcinoid, demonstrating
small, rounded, uniform cells.

74
TUMOR METASTASIS

Numerous metastases
from a renal cell
carcinoma

75
MALIGNANT MESOTHELIOMA
■ Asal : pleura viseral / parietal
■ Asbestos
■ Periode laten 25 – 45 tahun
■ Lesi yg difus, meluas pada rongga pleura,
efusi pleura ekstensif
■ Campuran 2 tipe sel: sel epitel & sel stroma
■ Epithelioid type & sarcomatoid type
■ Epithelioid mesothelioma dd/ adeno ca paru
■ Gold standard of diagnosis: electron
microscopy
76
Ultrastructural features of pulmonary adenocarcinoma (A), characterized by short,
plump microvilli, contrasted with those of mesothelioma (B), in which microvilli are
numerous, long, and slender 77
Malignant mesothelioma.
Note the thick, firm, white
pleural tumor tissue that
ensheathes this bisected
lung.

78
A, Malignant mesothelioma, epithelial type. B, Malignant
mesothelioma, mixed type, stained for calretinin (immunoper-
oxidase method). The epithelial component is
strongly positive (dark brown), while the sarcomatoid
component is less so.
79
■ Gejala klinis:
- nyeri dada
- sesak nafas
- efusi pleura berulang

80
Mediastinum

81
Thymus
■ Agenesis dan hipoplasia ok kegagalan
perkembangan komponen epitel atau limfoid.
■ Hiperplasia (berhubungan dengan penyakit
autoimun, tu myestenia gravis)
■ Hiperplasi sulit utk d dx/ dr ukuran atau
beratnya sj ( variasi pd papulasi umum)
■ Neoplasma

82
Thymic Neoplasm

■ Epitelial: thymoma, thymic ca

■ Lymphoid: Hodgkin & non Hodgkin’s
lymphoma
■ Germ cell: seminoma; teratoma
■ Stromal: thymolipoma
■ Lain2: thymic carcinoid; small cell ca

83
84
A well encapsulated type A thymoma with vaguely lobulated appearance and thin
white fibrous bands.

85
 A

Type A thymoma is composed of spindle cellls (A) or oval cells (B) with
bland nuclei arranged in solid sheets without any particular pattern (B) or
in a storiform patern (A).
86
A

A Macroscopic appearance of a
type AB thymoma showing
multiple nodules separated by
fibrous bands.
B Type AB thymoma composed
of lymphocyte-associated type B
nodules and diffuse
B
lymphocytepoor
type A areas.
87
88