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2017年1月5日 星期四

[醫如往常] Senior Clerkship Day 118: Pathology: Soft tissue tumor

Soft tissue tumor 李醫師
GIST Gastrointestinal stromal tumor
Stomach common
Vacuole nucleus
Cajal cell : c-kit RTK mutation-> cytoplasm也有
Exon 9, 11 most common
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Polygonal epithelial-like GIST
PDGFRA RTK mutation
Exon 12, 18
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HPF>20 mitosis
Size
Location: stomach prognosis good
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2nd resistance on c-kit
1st resistance on c-kit exon 13, 17


GIST的基因突變：
大約80%的GIST會有酪氨酸激酶受體KIT的致癌基因突變，目前已發現GIST的KIT有 5個不同外顯子(exon)的基因突變－exon 11 (67%), exon 9 (10%), and exons 8, 13, and 17 (3%)，而不同部位的GIST常表現不同KIT基因突變的變異，如：exon 8 (小腸)、exon 9 (小腸、大腸)、而exon 11, 13, 17 (所有部位)；另外約5～7%的GIST會有PDGFRA的基因突變在exon 12, 14和18的位置，通常發生在胃的GIST；然而，有10～15%的GIST臨床上無法測得KIT或PDGFRA的基因突變。

在Imitinib治療後exon 9突變的病人約2成會發展出2次的基因突變；而一開始為exon 11突變的病人則超過7成會產生2次的基因突變，而對Imitinib產生抗藥性。

Sunitinib (Sutent):為多靶標的酪氨酸激酶受體抑制劑（含：抑制PDGF和VEGF受體） ，其對exon 13或14突變的GIST具有療效，

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Melanoma, amelanotic type
Pagetoid spreading
c-kit +
S-100 +
EC junction, anorectal junction
Very rare


B-RAF
NF1
NRAS


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Sclerotic type well-differentiated liposarcoma
Spindle cell neoplasm
Omentum
Perigastric

dedifferentiated liposarcoma 可能並存
12q amplification
MDM2
CDK4
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Sarcomas of uncertain differentiation
Synovial sarcoma
Agrassive
t(X;18) SS18-SSX1 or SS18-SSX2 or SS18-SSX4
Biphasic pattern: spindle + gland
可以只有spindle

Ddx: GIST, MPNST

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Inflammatory pseudotumor; IPT
inflammatory myofibroblastic tumor; IMFT

borderline
multinucleated foreign body Giant cell
Lymphoplasma cells
Spindle cells (空亮的核, 明顯核仁)
Ganglion-like cells (myofibroblast)
clonal cytogenetic abnormalities involving 2p23 ALK1 staining in 40% of IMTs


Epithelial type: more aggressive

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ALK1
RTK, dimer
Over-expression, 不用ligand

常見於ATLL; Adult T-cell leukemia/lymphoma, neuroblastoma
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myxoid liposarcoma (MLS), the t(12;22)(q13;p12) 
Q13 CHOP
Q12 EWS

Alveolar rhabdomyosarcoma
PAX3 & FKHR (now known as FOXO1).



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[醫如往常] Senior Clerkship Day 118: Pathology: Collagen

 Collagen 郭醫師
  • Type I: skin, tendon, vascular ligature, organs, bone (main component of the organic part of bone)
  • Type II: cartilage (main collagenous component of cartilage)
  • Type III: reticulate (main component of reticular fibers), commonly found alongside type I.
  • Type IV: forms basal lamina, the epithelium-secreted layer of the basement membrane.
  • Type V: cell surfaces, hair and placenta
  • Type VII: anchor of epithelial cells


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Liver 4-6X chromosomes
Fresh-> oil red


Eosinophil 雙折光
mast cell 荷包蛋
Basophil 核被granules cover
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van Gieson's stain (double stain)
Acidic 環境下染collagen, 不染smooth muscle
Nuclear用Weigert's iron hematoxylin 才不會洗掉
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Masson trichrome (三種染劑)

Biebrich’s scarlet (猩紅)染所有的東西變成紅色
接著用conjunction with phosphotungstic (燐鎢酸) or phosphomolybdic acid (燐鉬酸)洗掉

最後染aniline blue (苯胺藍)
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[醫如往常] Senior Clerkship Day 117: Pathology: Post radiation sarcoma

Triple Cancer
SPC 吳醫師
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病人無法躺平
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Oral mass for 2 years
89 y/o woman1
1) Nasopharyngeal carcinoma, unknown stage and type, status post radiotherapy in 195X, 
2) Tongue cancer, squamous cell carcinoma, pT1N0M0 stage I, status post left partial glossectomy in 200X
3) Post-irradiation sarcoma, pT2, hospice care, with progression in 2016
4) Lung cancer, adenocarcionoma, early stage, status post lobectomy 15 years ago, 
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Radiation induced sarcoma
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Radiation induced encephalomalacia
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Lung lobectomy
Psmomma body
Lymphadenoma
NPC

CK5 6
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NPC

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Keratin

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Post radiation sarcoma
CK, pan CK, SMA, DESMIN, S 100, myogenin, H3k27me3 (-)

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CD99, INI1, p53, ki67 +
P16, HHV8, EBV -
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RIS
至少要照四年以上才會長
Mitosis
C myc gene
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[醫如往常] Senior Clerkship Day 117: Pathology: Cytology

Cytology
毛醫師

Exfoliative
Uterine
Endometrial

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Washing brushing

Aspiration
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病理部三種
Pap smear
Cell block

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Transformation zone
HPV
Columnar metaplasia to squamous

10顆良好的才是好片子
8000-12000顆細胞
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Liquid base
5000顆
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固定液95%酒精15-30min
Cytospin
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Cell block.   For pleura
10% formalin
Architecture
Special stain for tumor unknown origin
Eg Thyroid transcription factor 1 nuclear stain
Follicular cell, parafollicular cell

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On site cytology
Air dry cell inflation
Inclusion 比較清楚

Papanicolaou stain
Hematoxylin nuclear
OG  squamous orange
Light green cyanophilic NC ratio high cell
Eosin Y eosinophinic epithelium
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LSIl CIN 1
HSIL CIN 2/3

Low risk, mainly HPV 16
High risk , AIS.  HPV 16 mainly
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現在glandular type 越來越多

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Pap smear 台灣一年，而國外三年
HPV test + Pap smear  五年一次

Corposcope
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Koilocyte
Irregular nuclear
Multiple nucleus
Coarse chromatin
Irregular cell membrane thickness
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Squamous Intralepithilial lesion
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P53 E6
PRB E7 E2F
P16 staining cytoplasm and nuclear
Ki67 nuclear
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Liquid based prepararion
固定是用酒精
Remove mucus and blood
Further IHC p16, Ki67 double stain
Molecular studies
  • 20 mm Thinprep
  • SurePath, density sedimentation 13mm


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Bethesda system 2014

Organism
Candida
Trichomonas vaginalis

Endometrial cell >45 years
Out phase >10 days after menstruations

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[醫如往常] Senior Clerkship Day 120: Pathology: FISH

FISH 連醫師
Dapi bue
Texas red
Orange

10% area cluster
20顆平均
.
Her2 amplification>6
Her2, centromere>2

TDLU
Myoepi, p63 nuclear
Also prostate basal, PIN

Hepatocyte, renal tubule
emzyme
Background 很多雜值

Papillary 只有在乳癌有in situ
其他都直接代表invasive.
Breast要加上invasive才代表invasive


Defect size 外科拿走的部分

pTMN
ypTMN neoadjuvant

Onco type 21 mRNA, 分析化療利弊
Mamaprint 70






Metaplastic NTUH一年大概五個

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[醫如往常] Senior Clerkship Day 113, 115: Pathology: hematology

    Hematology 林醫師
    MDS; myelodysplastic syndrome
    Pancytopenia
    CD31 megaloblasts ↑
    Erythroid aplasia
    MPO<50%
    CD34 ↑
    CD117 ↑(membrane)
    tdt↑(nuclear)
    Ki-67↑

    要配合Peripheral blood，MPN周邊血球是多而成熟，MDS是cytopenia
    myeloproliferative neoplasms

    Diagnostic criteria for MDS/MPN with ring sideroblasts and thrombocytosis
    MDS/MPN diagnostic criteria
    • Anemia associated with erythroid lineage dysplasia with or without multilineage dysplasia, ≥15% ring sideroblasts,* <1% blasts in PB and <5% blasts in the BM
    • Persistent thrombocytosis with platelet count ≥450 × 109/L
    • Presence of a SF3B1 mutation or, in the absence of SF3B1 mutation, no history of recent cytotoxic or growth factor therapy that could explain the myelodysplastic/myeloproliferative features†
    • No BCR-ABL1 fusion gene, no rearrangement of PDGFRA, PDGFRB, or FGFR1; or PCM1-JAK2; no (3;3)(q21;q26), inv(3)(q21q26) or del(5q)‡
    • No preceding history of MPN, MDS (except MDS-RS), or other type of MDS/MPN
    • ↵* At least 15% ring sideroblasts required even if SF3B1 mutation is detected.
    • ↵† A diagnosis of MDS/MPN-RS-T is strongly supported by the presence of SF3B1 mutation together with a mutation in JAK2 V617F, CALR, or MPL genes.
    • ↵‡ In a case which otherwise fulfills the diagnostic criteria for MDS with isolated del(5q)-no or minimal absolute basophilia; basophils usually <2% of leukocytes.
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    PB and BM findings and cytogenetics of MDS
    Name
    Dysplastic lineages
    Cytopenias*
    Ring sideroblasts as % of marrow erythroid elements
    BM and PB blasts
    Cytogenetics by conventional karyotype analysis
    MDS with single lineage dysplasia (MDS-SLD)
    1
    1 or 2
    <15%/<5%†
    BM <5%, PB <1%, no Auer rods
    Any, unless fulfills all criteria for MDS with isolated del(5q)
    MDS with multilineage dysplasia (MDS-MLD)
    2 or 3
    1-3
    <15%/<5%†
    BM <5%, PB <1%, no Auer rods
    Any, unless fulfills all criteria for MDS with isolated del(5q)
    MDS with ring sideroblasts (MDS-RS)





    MDS-RS with single lineage dysplasia (MDS-RS-SLD)
    1
    1 or 2
    ≥15%/≥5%†
    BM <5%, PB <1%, no Auer rods
    Any, unless fulfills all criteria for MDS with isolated del(5q)
    MDS-RS with multilineage dysplasia (MDS-RS-MLD)
    2 or 3
    1-3
    ≥15%/≥5%†
    BM <5%, PB <1%, no Auer rods
    Any, unless fulfills all criteria for MDS with isolated del(5q)
    MDS with isolated del(5q)
    1-3
    1-2
    None or any
    BM <5%, PB <1%, no Auer rods
    del(5q) alone or with 1 additional abnormality except −7 or del(7q)
    MDS with excess blasts (MDS-EB)





    MDS-EB-1
    0-3
    1-3
    None or any
    BM 5%-9% or PB 2%-4%, no Auer rods
    Any
    MDS-EB-2
    0-3
    1-3
    None or any
    BM 10%-19% or PB 5%-19% or Auer rods
    Any
    MDS, unclassifiable (MDS-U)





    with 1% blood blasts
    1-3
    1-3
    None or any
    BM <5%, PB = 1%,‡ no Auer rods
    Any
    with single lineage dysplasia and pancytopenia
    1
    3
    None or any
    BM <5%, PB <1%, no Auer rods
    Any
    based on defining cytogenetic abnormality
    0
    1-3
    <15%§
    BM <5%, PB <1%, no Auer rods
    MDS-defining    abnormality
    Refractory cytopenia of childhood
    1-3
    1-3
    None
    BM <5%, PB <2%
    Any
    • ↵* Cytopenias defined as: hemoglobin, <10 g/dL; platelet count, <100 × 109/L; and absolute neutrophil count, <1.8 × 109/L. Rarely, MDS may present with mild anemia or thrombocytopenia above these levels. PB monocytes must be <1 × 109/L
    • ↵† If SF3B1 mutation is present.
    • ↵‡ One percent PB blasts must be recorded on at least 2 separate occasions.
    • ↵§ Cases with ≥15% ring sideroblasts by definition have significant erythroid dysplasia, and are classified as MDS-RS-SLD.



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    Myeloma
    CD138 plasma cell
    CD56 +/-
    CD79a -
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    Megalokaryocytes: CD31

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    Desmoplastic small round cell tumor
    WT1 +
    CK -
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    Diffuse large B cell
    Intra vascular
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    尤醫師
    Paracortex: T cells
    Mantle zone: naïve B
    Germinal center: hyperpigmentation, class swich
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    Low grade B cell lymphoma: Congo red +
    Follicular type: BCL6, CD10 (normal在neutrophil, stroma)
    Mantle zone: cyclinD1, CD5 (normal在T-cell)
    Marginal zone: CD43
    CLL: CD5, CD23 (normal在follicular dendritic cells)
    SLL
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     Chronic lymphocytic leukemia in (Richter's) transformation
    出現平常B cell沒有的CD43
    Germinal center 喪失bcl-2
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    Clusters of CD123 positive PDC were observed in Kikuchi's disease
    Post. neck
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    Asia nose necrosis->NK/T cell lymphoma
    Angiocentric pattern
    CD3 (cyto)
    CD5 (-)
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[醫如往常] Senior Clerkship Day 113: Pathology: sarcoma

    Microconference
    張醫師

    Ewing like sarcoma
    Round cell sarcoma
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    CIC rearranged sarcoma
    DUX4L
    T(4;19)
    T(10:19)

    Ddx: BCOR-CCMB3
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    CIC, Repressor in RTK
    DUX4 double homeobox

    ETV1,4, FEV

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    Young adult
    Soft tissue
    Chemoresistance
    Worse prognosis

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    Diffuse and lobular architecture
    Microcysts
    Myxoid
    Desmoplasia
    Vesical chromatin
    Amphophilic cytoplasm
    Geographic necrosis
    Perivascular cuff
    Vague storiform
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    Pleomorphism
    Prominent nucleoli
    Mitotic index
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    CD99在 Ewing sarcoma membrane
    Ewing 不會WT1

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    CIC1 sarcoma
    ETV4 87%+
    NKX2-2  -
    WT1 95+.  C-terminals
    ETV4 90%+
    Calretinin focal
    Cd99 focal
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    Ewing sarcoma
    CD99 +
    NKX2-2 84%+
    WT1 -
    ETV4 -
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    BCOR sarcoma
    CD99 -
    WT1 -
    ETV4 -
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    Unclassified round cell sarcoma

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    DUX4
    在B cell ALL , Rhabdomyosarcoma 也可能發現
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[醫如往常] Senior Clerkship Day 111: Pathology: Sclerosing mucoepidermoid carcinoma with eosinophilia

李醫師
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OCT
OCT frozen
optimum cutting temperature compound
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Fixation
Avoid autolysis, 防止微生物孳生
10% 中性福馬林 (4%甲醛)
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Dehydration
Alcohol
變形萎縮
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Clear 透明化
Xylene

折射率 1.494
蓋玻片 1.51
載玻片 1.52
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Infiltration
Paraffin
變形萎縮
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Embedding, casting, blocking
壓到最底部

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SPC李醫師
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63F
Neck swelling for 4 months
Abx was not effective
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Sclerosing mucoepidermoid carcinoma with eosinophilia
Right buccal region
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Mucous gland
Submandibular, submental gland like?

Minor salivary gland


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Tumor nest
Trabeculae, cord like pattern

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Keloid like collagen

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Tumor
Glandular structure
Mitosis

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CK7
P63
P5,6
IgG4

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Ddx
Kimura disease
用steroid 治療

Lymphoid nodular pattern
不會有tumor pattern, infiltrated pattern
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Sclerosing mucoepidermoid carcinoma



Japan

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P63 diffuse positive
Keratinazation


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