| What is neoplasia in general? | Cancer is caused by DNA mutation, done by exposure to mutagen or aging, we have epigenetic changes (methylation, histone modification) so different expression (growth, survival and senescence), genetic alterations in a cell are heritable to its daughter cells (Clonal)
Neoplasia (new growth) are cells that replicate w/out regulatory influences that act on mother cells that are normal (autonomous cells and increase in size regardless of environment) Neoplasm = tumor and relies on host nutrition and blood supply, some are benign and some are malignant |
| What is the difference between benign and malignant neoplasms? | Benign (microscopic, innocent, localized, removed surgically, pt survive, can produce morbidity or lethality sometimes)
Malignant (invade and destroy surrounding, spread distant, cause death, cancers, adhere close to any part they enter in contact with, not all lead to death)
Common features (two components, parenchyma (neoplastic cells, determine biologic behaviour) and host non-neoplastic stroma (CT, vessels and inflammatory cells, crucial for neoplasm growth) |
| What are benign tumors? | Omas (Fibroma, chondroma..), adenoma (epithelia produce gland like structures derived from glands lack glandular growth pattern,)
Papilloma (produce fingerlike fronds in epithelia), Polyps (not usually tumors more inflammatory, some are malignant tumors, mass above mucosal surface), Cystadenomas (hollow cystic masses, mostly in ovaries) |
| What are malignant tumors? | Non-epithelial tumors (Sarcomas (solid mesenchymal tissues, acc to cell type liposarcoma, chondrosarcoma ...)
Mesenchyma of blood (leukemia/ lymphomas)
Epithelial tumors (All three germ cell layers, all carcinomas, like renal tubular (mesoderm), skin (ectoderm) lining of gut (endoderm)) note that mesoderm gives carcinoma (epithelia), sarcoma (mesenchymal) and hematolymphoid (leukemia lymphoma)
Mixed tumors (monoclonal but differentiate into many lineages, salivary glands (pleomorphic adenoma) epithelia + fibromyxoid stroma, fibroadenoma of female breast (ductal elements (adenoma) + loose fibrous tissue (fibroma) |
| What are some other tumors? | Teratoma (mixed tumor mature + immature cells, one or more germ cell layers maybe three, totipotent germ cells (ovary/testes) that differentiate into any of cell types in body, resemble bone, epithelium, muscles..) |
| How is nomenclatures of some tumros? | Lymphoma, mesothelioma, melanoma, invasive meningioma and seminoma are malignant (not benign)
Hamartoma (mass of disorganized tissue acc to site, Hamartochonroma of lungs)
Choristoma (anomaly of heterotopic nest of cells, small nodule in pancreatic tissue may be submucosa of stomach, duodenum. |
| How is differentiation and anaplasia characteristics of benign and malignant tumors? | how much does neoplasm resemble original cells, if no differentiation: Anaplasia, benign neoplasms resemble normal cells (lipoma, chondroma), rare mitosis and normal configuration, malignant have morphologic alterations, some neoplasms are malignant though well-differentiated (like thyroid adenocarcinoma seen by invasion malignant), no difference in stroma, tumors of undifferentiated cells in anaplatic malignancy, loss of function of differentiated normal cells)
Anaplasia (pleomorphic, nuclear abnormalities, tumor giant cells, atypical mitosis, loss of polarity)
Functional properties are sustained in well-differentiated tumors while anaplastic are less likely to have function, endocrine tumors differentiated increase secretion, skin increase keratin, hepatocellular secrete bile, some produce fetal proteins (unanticipated), non-endocrine may produce ectopic hormones (paraneoplastic) |
| What is dysplasia? | Disordered proliferation, loss of uniformity of individual celsl in architecture, pleomorphic abnormally large hyperchromatic nuclei, more mitosis than usual in abnormal locations of epithelium, if severe and involves entire epithelium it is a carcinoma (preinvasive stage of cancer) |
| How is local invasion characteristic of benign and malignant tumor? | Growth of tumor accompanies infiltration, invasion and destruction of surrounding, most benign ones are localized and usually develop a rim of compressed fibrous tissues (capsule) made by fibroblast ECM activated by hypoxci damage to parenchymal cells from compression by expanding tumor, encapsulation makes tumor more easily removable and discrete.
Capsulation = benign, no capsule could be both, may be surrounded by compressed normal tissue (leiomyoma), some lack any demarcation (benign vascular neoplasms like hemangioma difficult to excise) |
| How is metastasis characteristic of of benign and malignant tumor? | Spread to tumor to site discontinuous w/primary tumor, marker of malignancy, invasiveness permits them to vessels and lymphatics and cavities, 30% pt w/solid mass have evident metastases, 20% have occult metastases.
More anaplastic more metastasis possible, exception are extremely small cancers metastasize.
Most malignant cancers metastasize but some infrequent (basal cell carcinoma of skin), most primary tumors of CNS undergo metastasis |
| What are pathways of metastasis of neoplasms? | Seeding w/in body cavity (invade body cavity, cancers of ovary invade peritoneum, or CNS neoplasm (medulloblastoma/ ependynoma) go to cerebral ventricles by CSF to meninges/ spinal cord)
Lymphatic spread (more typical, favored by sarcoma, pattern depends on site of tumor, lung carcinoma spread to regional bronchial nodes then hilar, breast go to axillary nodes, medial breast to nodes along internal mammary artery, and thus supra and infraclavicular nodes are seeded, some cases witness skip metastasis
Sentinel lymph node (first one to recieve tumor) can be identified by dyes near primary tumor, biopsy of it gives spread info use to plan tx, enlargement doesn't always mean metastasis)
Hematogenous spread (carcinoma, liver and lungs most frequent sites of metastasis here, near vertebra embolize through paravertebral plexus go to thyroid and prostate |
| What are environmental factors involved in neoplasia? | Seen by epidemiologic variations among countries (more environment than genetic)
Most imp (diet (obesity increase risk of many cancers), smoking (mouth, esophagus, larynx, pancreas, bladder, lung), Alcohol (oropharynx, larynx, esophagus, liver), infectious (15% of cancers WW) |
| What are some occupational cancers? | . |
| What is the relation between age and cancer? | Cancer frequency increases w/age in general, most occur age 55-75, explained by accumulation of somatic mutations leading to malignant neoplasms, and decline of immunity.
Although responsible for death of 10% children <15 years, major lethal ones are leukemias, CNS, lymphomas, soft tissue and bone sarcomas |
| What are some acquired predisposing conditions leads to neoplasia? | Disorders associated w/chronic inflammation (IBD, asbestosis, pancreatitis, cholecystitis, sjorgren, gastritis, hepatitis...) all can lead to carcinomas, mesothelioma or lymphoma (sjogren/ peptic ulcers))
Immunodeficiency state (virus-induced cancers, lymphoma and carcinoma and some sarcoma-like)
Precursor lesions (dysplasia, secondary to chronic inflammation or hormonal disturbance or spontaneous, progress to cancer inevitable important to recognize precursor lesion to remove and lower cancer risk) |
| What are most commonprecursor lesions? | Squamous metaplasia and dysplasia of bronchial mucosa (habitual smokers at risk for lung carcinoma)
Endometrial hyperplasia and dysplasia (women unopposed to estrogen stimulation, risk for endometrial carcinoma)
Leukoplakia of oral cavity/vulva/ penis could become squamous cell carcinoma
Note that Villous adenoma of colon is a precursor and precancerous condition |
| Are benign tumors precancerous lesions? | they are not in general w/exceptions, adenomas of colon can enlarge and become malignant (50%), malignancy change by leiomyocytes of uterus is very rare, risk of developing cancer depends on exposures and genetic variants. |
| What are cancer genes? | Genes affected by genetic aberration in cancer, could be acquired by environment, may occur spontaneously or germ line, numerous, 4 classes (oncogenes, tumor suppressor genes, apoptosis regulation genes, genes regulating interaction between cancer and normal cells.
Oncogenes (increase cell growth), tumor suppressor (prevent uncontrollable growth) Regulate apoptosis (enhancing cell survival), Interaction genes (tumor recognition by immune system)
Mostly acquired through life, but some are germ line (RB, TP53, CDKN2A, APC, NF1, NF2, MEN, RET, BRCA, MSH, PTCH..autodominant),(xeroderma pig, ataxia ATM, bloom BLM, Faconi anemia auto recessive) |
| What are the classes of mutations in cancers? | Driver (pathogenic, alter function of cancer gene giving cancer, acquired by gene rearrangments [overexpression, especially hematopoeitic like Burkitt lymphoma t(8:14) in more than 90%, overexpression of MYC], deletions [tumor suppressor, RB 13q14 retinoblastoma, 17P TP53], amplification [increases oncogenes, NMYC neuroblastoma, HER2 breast cancer])
Passenger (acquired mutations don't affect cell behavior, may become driver if pressure on tumor changes like medication)
Point mutations (can convert proto-oncogenes to oncogenes gain-of-function, like RAS gene, or loss-of-function like TP53 tumor suppressor gene)
Aneuploidy (seen in carcinoma, increase oncogenes (MYC) and decrease tumor suppressors (TP53)
miRNA (negative regulator of genes, leads to over and underproduction of oncogenes) |
| What are epigenetic modifications and cancer? | Tumor suppressor genes and DNA repair genes may be suppressed by epigenetic changes |
| How is carcinogenesis a multistep process? | Needs multiple mutations accumulating genetic alterations that transform the phenotype into cancer, cancers undergo darwinian selection and evolve, become more aggressive and malignant (tumor progression) so tumors become genetically heterogenous in presentation.
Darwinian evolution of cancer explains why cancers become more aggressive and less responsive to therapy (genetic heterogeneity and recurrence) |
| What are hallmarks of cancers? | 8 changes in physiology .
Self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, altered cellular metabolism, evasion of apoptosis, limitless replicative potential (immortality), sustained angiogenesis, invasion and metastasis, evasion of immune system.
All these may be accelerated by cancer promoting inflammation and genomic instability |
| How is self-sufficiency in growth signals in cancerous cells? | Proto-ocnogenes (normal cell genes, promote cell proliferation)
Oncogenes (overexpressed proto-oncogenes, no need for growth signals)
Oncoproteins (uncontrolled cell proliferation, express growth factors and its receptor (autocrine), encode TK, amplify EGF (HER2 in breast cancer), block hydrolysis of GTP unchecked signal (RAS), transcription factors unregulated, translocated MYC in lymphoma, mutation of cyclin genes uncontrolled cell cycle progress seen in melanoma, brain, lung, pancreatic cancer) |
| How is insensitivity to growth inhibitory signals by tumor suppressor genes? | RB gene (governs cell cycle), key in regulation of cell cycle, keep cell in G1 anti-proliferative gene (regulates G1/S checkpoint), central for malignant transformation, one of four regulators is mutated in most human cancer (p16, cyclin D, CDK4, RB), may occur by viral proteins targetting RB like HPV deletes RB function.
TP53 most common mutated gene in human cancer, p53 is suppressed and its function by CDKN1A transcription increase is G0 activation, induce permenant cell cycle arrest, and trigger apoptosis. stressed by DNA damage assist in repair and induce repair genes.
More than 70% of cancers are by mutation in p53, 30% of malignant have defective genes upstream./downstream of p53.
So RB external changes, p53 internal (DNA damage) also could be by HPV |
| How is altered cellular metabolism in cancer? | Warburg metabolism (pro-growth metabolism) induces exposure to GF, fixed in cancer cells due to driver mutations, oncogenes induce (RAS, MYC, GFR) and some inhibit (PTEN, NF1, p53 suppressors)
Cancer cells avoid autophagy by accumulating mutations. |
| How is evasion of apoptosis in cancer? | Loss of p53 function (TP53/ overexpression of MDM2), overexpression of anti-apoptotic members (BCL2).
So we can use inhibitos of MDM2 and BCL2 as therapy |
| How is limitless replicative potential immortality in cancer? | Tumor cells activate telomerase to achieve immortality |
| How is sustained angiogenesis in cancer? | in order for a tumor to enlarge more than 1-2 mm it needs angiogenesis, occurs by vessel-sprout from preexisting capillaries (neo-vascularization), endothelia newly made promote growth of tumors by secreting GF, vessels are leaky and dilated and have anarchic network.
Hypoxia usually triggers this angiogenesis by increasing angiogenic factors, by tumor cells or inflammatory cells or resident stromal cells
Factors regulating angiogenesis (p53 [angio inhibitor thrombospondin 1], RAS, MYC, MAPK upregulate VEGF, VEGF [inhibitors treat some cancers]) |
| How is invasion and metastasis in cancer? | Result from interaction between cancer cells, stromal cells, and ECM, start with local invasion to intravasation to blood and lymph, go through blood, extravasation from vessels, formation of micrometastasis, growth into macrometastasis.
May be interrupted by host/ tumor factors.
Carcinoma breaches basement membrane first, then ECM then circulation, can be resolved by loosening intercellular connections between tumor cells, local degradation of basement membrane, changes in attachment of tumor cells to ECM, locomotion
Tumor cells or tumor derived DNA go through blood, mostly as single cells and rare aggregating emboli, in blood they are vulnerable to degradation and don't proliferate.
Site of metastasis depends on location and tropism of tumor cells to specific places, frequent liver and lung all cancers,
Particular (prostate->bone, broncho->adrenals and brain, neuro->liver and bones |
| How is evasion of immune surviellence in cancer? | There are tumor antigens (may be mutated or increased normal proteins like tyrosine, or antigens expressed in inappropriate place like cancer-testis Ag, or viral proteins like EBV/HPV)
Normally cells should get destroyed by CD8 molecules attacking MHC I, which is evaded by PDL1 acting on PD1 of CTL leading to inhibition of CTL/ or CTLA4 also inhibits CTL interacting w/B7 Ag, so we are using Ab against those Ag in therapy |
| How is genomic instability as enabler of malignancy? | Mutations in DNA repair system predisposes cancer, HNPCC syndrome (defect in mismatch repair, develop carcinoma of colon (MSI)), Xeroderma pig (NER pathway mutation, skin cancer risk exposed to sunlight) Bloom syndrome, ataxia telangectasia, BRCA hypersensitivity to DNA damage. |
| What are the etiologies of cancer? | Carcinogenic agents (genetic damage, three agents:
Chemicals (no metabolic conversion direct carcinogenic, some are indirect acting need metabolic conversion, some are increased by admin of hormones (direct like alkylating agents and acetylating agents, indirect like polycyclic and aromatic HCs), highly reactive electrophile group)
Radiation carcinogenesis (ionizing cause chrms brake and rearrangement, UV forms dimers in DNA cause mutation (Squamous cell carcinoma/melanoma))
Oncogenic viruses and microbes (HTLV1 T cell leukemia by Tax protein, HPV causes benign warts and cervical cancer oncogenes p53 and RB, EBV Burkitt lymphoma, HepB and C hepatocellular carcinoma by Hbx Ag, H.pylori adenocarcinoma and MALToma by gastric cell proliferation |
| What are pretumoral lesions? | Elevated risk of cancer (Hamartoma, Burn scars, dystrophy (estrogen induced endometrial hyperplasia), Chronic inflammation, Viruses, Metaplasia (bronchial squamous cell metaplasia)
Precancerous dysplasia lesions (become cancerous by accumulation of genetic anomalies) |
| What is dysplasia? | Severity of dysplasia is graded more abnormality more dysplasia and closer to cancer.
Extreme (difficult to distinguish cancer in situ), mild moderate or severe, low/high grade, grade 1,2,3 intraepithelial neoplasia are all ways to grade dysplasia.
Epithelial dysplasia develops preferentially under certain conditions
pathological:
Gastric dysplasia develops preferentially in areas of intestinal metaplasia.
Dysplasia of the bronchial epithelium of smokers already modified by squamous metaplasia.
Dysplasia due to squamous metaplasia of the endocervix-ectocervix junction zone of the uterine cervix
(HPV).
Certain tumors considered benign have a risk of progressing towards
cancer in the absence of treatment: adenomas of the colon and rectum
N.B: Dysplasia can refer to certain anomalies in the development of an organ or part of an organ
(renal dysplasia, etc.) or a constitutional abnormality (bone dysplasia, etc.) |
| How is cancer in situ? | AKA intraepithelial carcinoma/non-invasive, proliferation of malignant epithelia not crossing basement membrane, application in tumors of covering, separated from vascularized CT by basement membrane, seen in squamous cells of vagina, skin, esophagus, squamous epithelium of bronchi, paramalpigean of bladder, glandular (mammary), digestive mucus membranes.
Usually not sarcoma (only theory), but malignant melanoma there are many in situ (intraepidermal melanoma/ SSM)
Screening is important for tx, can remain in situ for years, but if untreated it will become invasive. |
| What are the clinical aspects of neoplasia? | Benign and malignant may cause problems in location and impact adjacent structures, functional activity such as hormone synthesis or paraneoplastic syndrome, bleeding and infections if it ulcerates through surfaces, symptoms of rupture and infarction, cachexia. |
| What are effects of tumor on host? | Location is crucial (small pituitary adenoma compress surrounding cause hypopituitarism, 0.5 cm leiomyoma in wall of renal artery reduces blood supply cause HTN and renal ischemia, small common bile duct carcinoma causes biliary obstruction)
Hormone overproduction (adenoma/carcinoma of beta cells cause hyperinsulinism (maybe fatal), adrenal cortex adenomas increase steroids (aldosterone))
Tumor could get into gut cause intestinal obstruction/ infarction/ intussuception. |
| What is cancer cachexia? | Progressive loss of body fat and mass w/weakness, anorexia, anemia. Not caused by nutritional demand of tumor, results from soluble factors like cytokines. |
| What is paraneoplastic syndrome? | Symptoms not explained by metastasis or hormones, 10-15% of cancers, early manifestation of occult neoplasm, significant illness and lethal, may mimin metastasis.
Most common is hypercalcemia, Cushing's, non bacterial thrombotic endocarditis. Most associated are lung and breast cancers and hematologic malignancies.
Hypercalcemia most due to PTHrP formation by tumor cells, Cushings due to ectopic ACTH, hypercoagulability possible |
| How is grading and staging of cancer? | Level of differentiation (histology) is grade, extent of spread is stage.
Staging is more important clinically
Grade (low grade and high grade, like SBR in breast cancer we have 3 scores to get grade, Gleason in prostate cancer x+y score)
Staging (TNM, AJCC) |
| How is lab diagnosis of cancer? | Morphologic methods, Tumor markers, Molecular dx, Molecular profiling of Tumors (future of dx) |
| What are morphologic methods of diagnosing cancer? | We see benign and malignant, but middle not very much, clinical and radio not optimal, radiation induced changes can be similar to tumors, sections of healing fracture can mimic osteosarcoma, best is to get specimen (excision, FNA, cytologic smear)
Frozen section (determine nature of mass lesion, evaluate lymph nodes, quick frozen section gets evaluation w/in minutes)
FNA (cytologic exam after aspiration, more for palpable lesions like thyroid, breast, nodes, salivary glands, some deeper like liver, pancreas, pelvis nodes)
Cytologic smears (PAP for cervix, liquids (CSF, abdominal), neoplasms are shed into liquid) |
| How is immunohistochemistry used in cancer dx? | Powerful, determines origin of metastasis, like cytokeratin differentiate large cell lymphoma than undifferentiated carcinoma, PSA in prostatic origin. Some therapeutic like immunocytochemical detection of ER/PR in breast cancer.
Use monoclonal Ab specific for cellular component, all serum markers, Tg, S100 (melanoma), Actin (muscle), CD (lymphoma), estrogen receptor (breast cancer), intermediate filaments. |
| How is molecular investiga tion in cancer dx? | PCR of T cells and B cells/Igs monoclonal or polyclonal, FISH also used to see translocation in Ewing sarcoma.
Prognosis (Some have poor prognosis, FISH and PCR deect oncogenes HER2/NMYC)
Detection of minimal residual disease (BCR-ABL transcript by PCR measures residual chronic myeloid leukemia)
Diagnosis of Heriditary Predisposition to cancer (BRCA1, use it for prophylactic surgery/control)
Therapeutic-Decision making (according to mutation some respond to BRAF inhibitors (Melanoma) others no response) |
| What are epithelial tumors? | In epithelia (squamous, glandular, urothelial or endocrine tumors w/nosological problems of their own)
Mapligean (benign (papilloma, condyloma) Malignant (cutaneous carcinoma, epidermdoid/mucosa carcinoma))
Glandular (Colorectal, macrocommun, parenchymal tissues (macrocommun, mammary))
Endocrine (differentiated endocrine, morphologic malignancy) |
| What are the macroscopic aspects of epithelial carcinomas? | Coating epithelial tumors (Budding tumor (hollow organ), ulcerative tumor or infiltrating tumor, usually all seen in same tumor (colon and gastric see ulcerative, infitrative and budding))
Solid organ epithelial tumors (parenchymal, see nodule/mass, stellar infiltrative form reaching large area of organ or cystic form in pancreas, ovaries...) |
| What are histologic appearances of epithelial tumors? | Benign Papilloma (polypoid, exophytic, raspberry mucosa, skin or mucosa, viral origin (HPV), benign preserve architecture, basement membrane, no atypia but more mitosis, keratotic maturation normal)
Condyloma (squamous mucosa, HPV, STD, genitals and anorectal, acuminates (cauliflower) squamous proliferation increase in CT volume and cytopathy, sometimes multiple, most are benign and no recurrence, some progress to squamous cell carcinoma in pancreas)
Squamous cell carcinoma (in skin, buccopharynx, vagina, cervix, and metaplastic seen in bronchial squamous cell)
Tumors related to squamous cell carcinoma (similar to epidermal basal layer, slow local evolution, never metastasis)
Glandular epithelia tumors
Undifferentiated carcinomas |
| How are glandular epithelial tumors? | Frequent tumors, hollow organs and parenchyma, benign or malignant
Benign (adenomas [very differentiated, single mass rounded capsulated, can be cystadenoma, homogenous w/surrounding])
Malignant (Adenocarcinoma [mucosal, exocrine tubular, endocrine resemble normal gland])
Notion of differentiation (good proliferation resembles original tissue, bad absent characters on HE but demonstrated by histochemsitry/ IHC |
| How are urothelial/ transitional tumors? | In transitional epithelium of UTI, pelvis, ureters, bladder, men after 40 usually, risk factors include tobacco, occupational exposure (aniline) clinical presentation w/hematuria and voiding disorders (pollakiuria, voiding burn)
75% papillary vegetative aspect, aggressive acc to cytology grade (differentiation) and stage (infiltration).
Classified into papillary tumors w/low malignancy, low grade carcinoma and high grade carcinoma.
Usually if no infiltrate we just remove the tumor, if papillary tumor recurr we have risk of worsening and infiltration, if infiltration occurs we remove the bladder (cystectomy), and 15% infiltrate to outset and gets metastasized, they may result from flat lesions of carcinoma in situ so we should monitor by US, cytology (CIS) |
| How are tumors w/endocrine differentiation? | Either from endocrine glands or diffuse endocrine system, may be non-functional or hyperfunctional (ectopic secretion), diffuse in digestive tract, lungs, pancreas (alot), thymus, bile duct, thyroid calcitonin cells, ovaries, cervix, skin |
| How are undifferentiated carcinomas? | Cells are isolated or grouped, no maturation/secretion allow us to determine the type (adenocarcinoma/ squamous cell carcinoma), dx immunohistochemistry, may be epithelial origin and metastasis determining proper treatment. |
| Give some benign and malignant epithelial cell carcinoma? | . |
| What are sarcomas? | rare tumors, much less common than benign CT tumros and carcinomas, numerous varieties, rapid development w/local extension and hematogenous metastasis, nodular or infiltrating extravisceral CT soft tissues/bone/ viscera,
Detected by genomic abnormalities
Types (fibrosarcoma, osteosarcoma, chondrosarcoma, liposarcoma, rhabdomyosarcoma, angiosarcoma, leiomyosarcoma |
| What are malignant hemopathies? | Myeloid (AML, myeloproliferative neoplasms, myelodysplastic syndromes).
Lymphoid (LAL, Hodgkins and non-Hodgkins lymphoma)
Histiocytic proliferation, mastocystosis |
| What are malignant hemopathies and Lymphomas? | Non Hodgkins (B or T, high (large lymphocytes) or low grade) may be diffuse or nodular (follicular organization)
Hodgkins (monstrous tumor cells seen by Reed-Sternberg cells B lymphoid cell derived from germinal center.
Lymphomas (variable aggressiveness, needs histo for dx, immuno + biomol + cytogenetics, most frequent in nodes, but can be extra-ganglionic sites, complex classification, |
| What is mastocytosis? | Abnormal mast cell infiltrate, cutaneous or systemic, hetergenous w/ manifestations from skin lesions to aggressive neoplasms associated w/multiorgan failure and poor survival |
| What are other non-epithelial neoplasms? | Melanomas (cutaneous or extracutaneos), mesotheliomas, nerve tumors (shwannoma, NB, glioblastoma), germinal cell tumors, Blasteme tumors. |
| What are melanocytic tumors? | Benign tumor (naevocellular naevus) proliferated naevic cells, small rounded eosinophilic cytoplasm w/melanin pigments, grouped into theca cells or sheets of cells going to dermis, benign if (good individualization of theca, absence of inflammatory infiltrate, presence of vertical ripening gradient, atypica and mitosis presence
Melanoma (risk factors is light skin and sun exposure, initial phase of horizental extesion (intra epidermal) then vertical (infiltration of dermis), degree of dermal infiltration gives prognosis (thickness = Breslow index), aggressive tumors w/high risk of lymph node and visceral metastases. |
| What are mesotheliomas? | Benign pleural tumors (mesothelium) rare, malignant mainly pleural (maybe pericardial...) linked to asbestos exposure, give early parietal mesothelial proliferation, massive involvement of pleura formation of nodules and multiple masses, rapid fatality, biphasic proliferation of spindle cells and epithelial slits.
Dx by immunohistochemistry and rules out metastasis |
| What are germ cell tumors? | Rare (95% of testicular tumors but 1% of cancer in men), much rare in women, young pt, detected by serum markers, curable even metastatic, reproduce during embryogenesis observed.
Classifications include (seminoma, embryonal carcinoma, teratoma, yolk sac tumors, choriocarcinoma, complex germ cell tumors).
Testicular tumors (50% seminoma and 50% non seminoma, peak of seminoma in age 30, curable by surgery and radio, nonseminoma age 20, we see elevation of serum markers (aFP yolk tumors, bHCG choriocarcinoma) curable by chemotherapy)
Ovarian tumors (exceptionally malignant, dermoid cyst and complex teratoma frequent in ovary)
Extragonadic germ cell tumors (all germ cell tumors seen) |
| What is seminoma? | Dysgerminoma in the ovary or Germinoma in the intracerebral), It is the germ cell tumor with the greatest morphological similarity to the gonies (spermatogonia and oogonia).
Macroscopy : solid well limited, white tumor
Histologie : round large cells, monomorphe, with
clear or eosinphilic cytoplasme, central nuclei,
prominent nucleoli, Lymhocyte rich stroma |
| What are tumors of CNS and PNS? | A. Peripheral nerve Tumors
B. Peripheral Neuroblastomas
C. Peripheral neuro ectodermal tumors (PNET)
D. Primitive central nervous system tumor |
| What are CNS tumors? | Gliomas (very limited and some are benign (curable by resection/ localized tx), others infiltrating and progress w/years w/recurrence, others are aggressive, rapid growth fatal malignancy (glioblastoma), in children blastomas (neuroectodermal) seen in CNS, also grouped in PNET neuroblastoma (hemispherical) or medulloblastoma (cerebella))
Astrocytoma (low grade Astrocytoma presenting as an enlarged area of white matter in the left cerebral hemisphere)
Glioblastoma (Infiltrating, hemorrhagic and necrotic tumor mass. Tumor is densely cellular with tumor cells ,arranging in palisades around areas of necrosis) |
| What are tumors of blastema? | Made up of immature cells similar to those derived from the embryonic development (blastema) of a full tissue organ, appear most often in childhood, often very fast growing, prognosis depends on age and stage, Sometimes able to mature under the effects of chemotherapy.
The most frequent are :
Nephroblastoma, Neuroblastoma
Histologically, these tumors mimic the appearance of a blastema, and combine:
Undifferentiated blastematous areas, made of sheets of "small round and blue cells“
With Differentiated blastematous areas: differentiation varies according to the type of blastema: epithelial (primary renal tubes in a nephroblastoma), neuronal (in a neuroblastoma) or mesenchymal (muscle differentiation in certain nephroblastomas or medulloblastomas) |
