Precancers. Dysplaisa of squamous and glandular epithelium Flashcards
definition of precancer
on-invasive lesion that has genetic abnormalities, loss of cellular control funciton and some phenotypic charchterisitc of inavsive cancer, and is very likely to develop tint inasvive canver
or
genetically induved, non invasive lesion which with some probability leads to development of malignancy
criteria of precancer
- evidence exista thta precancer is associated with increased risk of cancer
- when precancer progresses to cancer, the resulting cnacer arises from cells
- precancer is different form normal tissye it arises form
- precancer is different form the cnacer into which it develops
- there are methods by which is can be diagnosed
inborn syndromes with high risk of malignancy
Li fraumeni s.: defect of p53
lynch s: defect of DNA repair genes
immunodeficinect
ecposition to carcinogens
disorder with high risk of developmetn of malignancy
cholescystolithasis
cryptorchidism (undescended testicle)
feature of clinical manifestation of malignancy-paraneoplastic phenoma
what is dysplasisa
- most common morphological featur eof precancer
-disturbances of normal tissue structure or normal cell morpholgy
-cells are larger, nuceli are larger aka increased N:C ratio, pleomorphism of cells and distinct nucleoli and so one
-can be reversible
what is reactive chnages
rversible chnages of tissue by injury, morphologically mimicking true dysplasia, distinguishing reactive atypia form true dysplasia can be difficul or immpossible
- these are seriously altered morpholoy
- ## not DNA induced lesions, only DIRECT INJURY OF TISSUE
hyperplasia
-progressive chnage in which ther eis increased number of cells in tissye
-pathological hyperplasia can develop into malognancy like of Lymphoid tissue in AIS, HP, induced MALT hyperplasia, atypical ductal hyperplasia in breats
- AIDS thing can bear risk of lymphoma–>precancerous
-gastritis of endometrial mucosa=MOST COMMON kind which is precancerous lesion
metaplasia
change of one differentiated tupe of tissye to antoher differentiated type of tissye
what is most crucial feature of precancerous
invasive growth/ infiltration
- It is a non-invasive lesion. it doesnt infiltrate
it is DNA induced
info about cells of precancerous
- are active and are able to proliferate withoug growth support
- proliferaet and growth is automatic(autonomous)
classification of precancers-according to importance
- stacionar/facultative
- progredient/obligatory
- absolute progredient precancers
stacionar/facultative
-transformation <20% of lesions, time inetrval >5y
-usually chronic tissueirritation-resp chronic proliferation of cells
-neurofibromatosis, endometrial hyperplasia
-not true precancers, only diseases which high tisk of mlignancy exceot the two mentioned
progredient/obligatiory
- transformation >20% of lesion, time interval <5y
- serous alteration of genetif information
-cornu cutaneum, cervical intraepithelial neoplasin-cin, prostatic intraepileila neoplasia-PIN, atypical endometrial hyperplasia
absolute progredient precancers
-100% occurence of malignancy
-FAP-familial adenomatous polyposis, XP-ceroderma pigmentosum
classifciation of precancers to morphology and development
- acquired microscopic precancers
- acquired large lesions with morphologic atypia
- precursors lesion occuring with inherited hyperplasic syndorme thta often progress into cancer
- acquired diffuse hyperplasia and diffuse metaplasia
acquired microscopic precancers
-msot commen
-mainly intraepi neoplasia
-need time to developm bc acc of DNA mutations
- multifocal lesions, atypical cells replace epi without formation of distinct tumor mass
baretts esophagus-only metaplasia
acquired large lesions with morphologic atypia
- often without lesions(dont chnage their apperance)
- macroscopic visbile mass,
- crowding of cells, irregualr growth pattern, marked cellular atypia , usually displastic cells
-irreversible
precursors lesion occuring with inherited hyperplasic syndorme thta often progress into cancer
- inborn muation
-casual genetic mutation
-younger people
-hyperplasia of cells without serious dysokasia
-usually multiple/resp. bilateral: in all kinds of tissye, basically 2 sided organs the tumors will occur in both sides (bilat)
-EX
A. multiple nedocrine neoplasia syndorme(MEN:hyperplasia of endrodrine cells in GITS–>increased nr cells..>neuroendocrine tumors
B. herediatry medullary thyroid carcinoma: hyperplasia of parafollicular cells which produce calcitonin–>attach both lobes of TG bilaterally
acquired diffuse hyperplasia and diffuse metaplasia
-diffuse chnage of mucosa/organ
-affect all teh tissue, not focal lesion
- increased nr cells, enlargment of tissue structures,, chnage of cells/tissue without serous dysplasia
-irrverible
-ex: endometrial hyperplasia
carcinogenesis- two basic types of mutations
causal and accompanying
causal (drivers)
- these mutations affect the genes whoch really progress to canver=responsible for carcnogenesis
- on or severl needed
-oncogene: normal genes in our body which reg increased proliferation of cells when needed
-antionocgne: normal which suppress prolif of cells
ypes of causal mutation
activation of oncogenes
inhibition of anti-oncogene
ianctivation of apoptosis
inactivation of DNA repair
accompanied(passengers)
precancers number
2-4 in precancerous
3-5 in carcinogenesis
invasive malignancy: 4-6 causal genetic mutationa +genetic instavbility
precancer is a …
genetic stable lesion
hematologic neoplasma
-only malignant
-usually only one cadual muattion charcteristic for distinct malignancy(bcr/abl)–>CML–>FL–>MCL–>AML-M3
chronic myelegenous leukemia has bcr/abl translocation(philadelphia chromosome)
follicular lymohima has translocation form chromosome 14–>18
hemopoiesis/ lymphopoiesis
- high cell prolifeation
- spread into peripheral blood(metastasing)
- infiltartion of organs
persistnece
-most of prescancers
-patinet ill get it and die with it
progression
-cells toward malignancy by acc of new DNA muation–>carcninogenesis
- cytological atypisa, mitotix act, formaiton of multiple lesions
regression
-mechnism: increased antigenicity of cells and increased apoptosis of cells
diagnosis of precancers by morphology
1) epithelial lesions
- most common
-clearly defined architerctur
-distrubances of cell stratification, differentiation, shape and size, chnages of cell nuclei(hyperchromia, pleomorphy, nucleoli), mitotic activity
- cells on BM-limiting facotr of infiltration
2)mesenchumal
- absence of BM
- criteria of assesment of dignity: size and nr of lesion, pleomorpjology of cells, number of cells, mititic act, necrosis
importance of precancer diagnostic
- early detection of precancer
-you have time to influence - cnacerogenesis is dynamic process: can be stopped or reversed
- possibilities for therapy
-like surgery
actinic keratosis/squamos cell carcinoma in situ
Bowens precancer
squamous carcinoma of skin
atypical endometrial hyperplasia
endometrioid adenocarcinoma
myelodysplastoc syndorme
leukemia
progressive transformaiton of germinal centers
lymphocyte predominant Hodgkins disease
