This document contains a summary of the lectures given in the course (principles and practice of ) Human Pathology Theme 1 Neoplasia. With this document I obtained a grade of 7,5. The document is clearly structured with a table of contents, and contains pictures for better understanding.
Legenda:
Nagekeken
Vraag over
Informatie over exam
Inhoudsopgave
LC 1.1 Pathology of primary skin tumors – Part 1 & 2 ............................................................................ 2
Neoplasia ............................................................................................................................................ 2
Skin cancer .......................................................................................................................................... 3
Clinical pathology ................................................................................................................................ 3
LC 1.2 Pathology of primary skin tumors – Part 2................................................................................... 4
Examples of skin tumors ..................................................................................................................... 4
Coursebook Neoplasia ............................................................................................................................ 8
Section 1: biology, histology and molecular pathology of skin tumors .............................................. 8
Case study ....................................................................................................................................... 8
SA 1.2A .......................................................................................................................................... 11
Diagnosis ISA 1.2 ........................................................................................................................... 12
SA 1.2B .......................................................................................................................................... 12
LS 1.1.1 .......................................................................................................................................... 14
LS 1.1.2 .......................................................................................................................................... 14
LC 1.3 Molecular pathology: Gene mutations in tumors ...................................................................... 14
LC 1.4 Molecular pathology: Chromosomal Aberrations ...................................................................... 17
Translocations ................................................................................................................................... 17
Copy number alterations (CNV): amplifications or losses of genes.................................................. 18
Coursebook Neoplasia .......................................................................................................................... 19
Section 2: molecular diagnostics in pathology, general ................................................................... 19
Rubin’s pathology Chapter 5 ......................................................................................................... 19
SA 1.3: proto-oncogenes and tumor suppressor genes................................................................ 20
Virtual work group ................................................................................................................................ 22
Case study 1 ...................................................................................................................................... 22
Case study 2 ...................................................................................................................................... 25
LC 1.5 Molecular pathology: Hematopathology ................................................................................... 26
LC 1.6 Molecular pathology: Molecular Diagnostics for Lymphomas .................................................. 28
Coursebook Neoplasia .......................................................................................................................... 29
Section 3: molecular pathology, molecular background and diagnosis of heamatological
malignancies ..................................................................................................................................... 29
, SA 1.4: lymphoma diagnostics, IG/TR clonality analysis as supplementary tool .......................... 29
Case study 3 .................................................................................................................................. 30
LC 1.7 & 1.8 Pathophysiology of Cervical Cancer.................................................................................. 32
Coursebook Neoplasia .......................................................................................................................... 37
Section 4: squamous cell carcinoma ................................................................................................. 37
SA 1.5: squamous cell carcinoma of the cervix ............................................................................. 37
SA 1.6: the cervical smear ............................................................................................................. 39
PC 1.1 Squamous Cell Carcinoma ......................................................................................................... 39
LC 1.1 Pathology of primary skin tumors – Part 1 & 2
Avital Amir, clinical pathologist Radboud UMC
Neoplasia
A neoplasm is a type of abnormal and excessive growth of tissue
Neoplasm: a genetically driven growth of cells (benign, pre-malignant or malignant)
Benign tumor: slowly growing mass, local growth, no metastases, cells don’t show atypia/anaplasia
(stop looking like precursor cells)
Dysplasia = abnormal growth or development of cells or organs with atypia/anaplasia (no mass ->
when it becomes a mass it’s a malignant tumor)
Malignant: rapid growth/proliferation of mass, infiltration in other tissues, metastasis, atypical cells
(don’t look like their precursor cells (voorlopercellen)
,Development of cancer
Multiple genetic aberrations in different genes, usually at least 6 genes
1. Autonomous cell proliferation: growth
2. New vessels formation: growth
3. Loss of programmed cell death (apoptosis): growth survival
4. Loss of differentiation: loss of function
5. Loss of cell contact inhibition: invasion
6. Growth into and out of vessels: metastasis
Genes involved in cancer formation
1. Oncogenes: code cell growth promoting proteins
a. Alteration: gain of function
2. Tumor suppressor genes: code inhibiting cell proliferating or apoptosis inducing proteins
a. Both alleles should be hit
3. DNA repair genes: control the genome/ repair DNA replication errors
a. Alteration: loss of function/ loss of gene/ loss of expression
b. Both alleles should be hit
Kinds of genetic alterations
1. Mutations (small 1 or few nucleotide changes): leads to activation of oncogenes (driver
BRAF/NRAS), loss of function/expression of tumor suppressor genes
2. Copy number variations (large): gain of oncogenes or loss of tumor suppressor genes
3. Chromosomal translocations (large): translocation (part of chromosome to other
chromosome) -> activation of oncogenes
Somatic mutation: acquired during life by carcinogen e.g. only present in those cells
Germline mutations: congenital, present in all cells of the body, can give susceptibility (gevoeligheid)
for cancer by mutation in second allele
Skin cancer
52% cases of skin cancer from all cancers in the Netherlands, then breast cancer 12% and then colon
cancer 11%.
Incidence of skin cancer is rising fast = epidemic
- Cause of this increase is: skin is largest organ, aging of the population, lifelong exposure to
UV light
Every cancer has its own mutational signature. UV light signature 7: CC is replaced by TT
Other causes of skin cancer: viral infection (HPV) and hereditary
Clinical pathology
What does a clinical pathologist do? A medical specialist who diagnoses disease by investigating
tissues. Macroscopy with naked eye, processed and prepared for microscopy (done by clinician’s and
not by pathologists). Fixed with formalin, dye cutting marges, cut relevant material with bread loaf
technique, in cassette, in paraffin, cut with microtome, on slide, staining, investigate microscopic
pictures in computer, make diagnosis
, Pathological investigation of (skin) tumors
1. Assessment of line of differentiation: from which tissue/cells is the tumor derived
2. Establish benign or malignant
3. Diagnosis
4. Determine stage of tumor (invasion depth)
5. Establish whether the margins are free of tumor
- Routine histology (H&E) sufficient in most cases
- Immunohistochemistry (10-15%)
o Use of antibody directed against antigen on a (tumor) cell. Visualized with
chromogen (from soluble to insoluble stain on section). E.g. staining with P16 (tumor
suppressor), when loss of P16 -> no staining -> malignant
- Molecular pathology (<2%); looking at DNA and RNA
o What are the treatment options e.g. specific targeted therapy
o How many copy number variations are present -> benign or malignant tumor
Wart (wrat): papillary mass of benign tumor
LC 1.2 Pathology of primary skin tumors – Part 2
Examples of skin tumors
Basel cell carcinoma BCC (by far most frequent 40%). Derived from hair follicle, basaloid cells.
- Often clefting (space around tumor) present
- Caused by UVB (sun-exposed sites and UV-specific mutations)
- Age mostly >40
- Caucasians
- Areas with cumulative sun-exposition (face)
- Clinical behavior
o Locally very aggressive
o Can be mutilating
o Hardly ever metastasizes
- Location
o Present in skin, not other organs
o Frequently around eyes and nose
o Not in mucosa, palm and soles (no hair follicles present)
Squamous cell carcinoma SCC (also rising fast)
- Derived from epidermis/keratinocytes are precursor cells
- Areas with cumulative sun-exposition (face)
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