Neoplasm's are also known as tumors (swelling) but all swellings are not neoplasms e.g. parasitic nodules, cold abscesses, chronic inflammations(tuberculosis, glanders). These swellings subside after the causative agent is removed while neoplasms grow continuously & indefinitely.
In inflammation and repair cells proliferate; but then there is a purpose for proliferation i.e. to protect and replace tissues. As soon as the need is fulfilled proliferation ceases and growth even regresses.
Neoplasm and hyperplasia
Hyperplasia results due to proliferation of cells of tissues from a definite demand. E.g. proliferation of surviving cells in a excised or damaged liver or kidney, erythropoietic tissue in anemia, hyperplasia of leucopoitic tissue during acute inflamation resulting into leucocytosis, thyroid gland in goitre, of mammary gland and prostrate when respective hormones are in excess.
In hyperplasia proliferation of cells is limited in “duration and amount”. It only progresses so long as the functional need or hormonal stimulus which evoked it persists.
In neoplasms no exciting cause can be identified.
In hyperplasia cells are typical of the parent cells, i.e. differentiated and of regular size and shape while in neoplasia cells are atypical, undifferentiated, anaplastic or pleomorphic.
In hyperplasia cells are organized and coordinate with the function of the parent tissue, while in neoplasia cells are disorganized and are not functionally in union with the normal tissue-autonomous.
Metastasis not present in hyperplasia.
From clinical point of view neoplasms are classified
on behaviouristic basis into; Benign (innocent) & Malignant.
Mammary gland Cancer
Head & Neck Cancer
Skin Cancer – Melanoma
Mast cell tumor in a dog & after its removal Hemangiopericytoma in a dog
Warts on udder of a cow Warts on body of a antelope
Mammary tumor in a bitch warts/pappiloma’s
Facial tumors in a Tasmanian devil
Osteosarcoma in a cow
Carcinoma: Malignant tumors derived from epithelial cells.
Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
Lymphoma and leukemia : Malignancies derived from hematopoietic (blood-forming) cells.
Blastic tumor or blastoma: A tumor (usually malignant) which resembles an immature or embryonic tissue e.g. dermoid cyst.
Adenoma : benign tumor of glandular origin.
Adenocarcinoma : malignant tumor of glandular epithelium.
Malignant tumors (cancers) are usually named using -carcinoma , -sarcoma or -blastoma as a suffix.
Benign tumors (which are not cancers) are named using -oma as a suffix.
Screening : a test done on healthy people to detect tumors before they become apparent.
Diagnosis : the confirmation of the cancerous nature of a lump.
Median survival time : a period of time, often measured in months or years, over which 50% of the cancer patients are expected to be alive.
Adjuvant therapy: treatment, either chemotherapy or radiation therapy, given after surgery to kill the remaining cancer cells.
Prognosis : the probability of cure after the therapy.
Pre-malignancy , pre-cancer or non-invasive tumor: A neoplasm that is not invasive but has the potential to progress to cancer (become invasive) if left untreated.
Stage : a number (usually on a scale of 4) established by the oncologist to describe the degree of invasion of the body by the tumor.
Recurrence : new tumors that appear at the site of the original tumor after surgery.
What is their Etiology ?
Divided into predisposing/intrinsic causes and exciting causes;
1 . Hereditary factors ;-
some tumors are common in some familial lines or particular breed of animal e.g. adeno-carcinoma in boxer, squamous cell carcinoma in white cats. Brachycephalic dogs develop more mast cell tumors.
2. Age ;-
Both dog and cats show high risk of tumors with increasing age.
3. sex ;-
Male dogs have 2.4 times greater risk of dev. malignant tumors of buccal cavity than females .
4. size :-
Giant breeds of dog develop osteogenic sarcomas.
5. colour :-
Dark breeds of dog develop malignant melanoma more often than light breeds .
6. species ;-
dogs have the widest spectrum of all tumor types observed in domestic animals.
7. Hormones ;-
Mammary gland, uterus, prostrate & the thyroid are active control of their hormones for normal cellular & functional activities leading to frank hyperplasia which ultimately becomes neoplastic.
Prolonged injections of estrogen causes mammary tumor in mice & uterine cancer in human females.
Basic structure of estrogens, progesterone, testosterone & adrenocorticoids is similar to benzanthracene & benzypyrene which are powerful carcinogens.
Exciting causes ;-
1.Oncogenic viruses :-
Oncogenic RNA viruses like Feline leukemia virus transmitted horizontally and having reverse transcriptase enzyme make DNA copies from viral RNA & incorporate it into host cell DNA for replication & cells may get transformed causing lymphoma, erythroleukomia and myeloproliferative diseases, Feline sarcoma virus, avain sarcoma virus, avain leucosis virus
oncogenic DNA viruses like canine oral papilloma virus causes multiple wart like masses on the mucous membranes and tongues of dogs on contact, papovavirus cause cutaneous papilomas in dog.
UV-radiation from sun is the only significant form of radiation causing spontaneous cancer in domestic animals. White cats, collie & Shetland sheepdog are susceptible to UV-radiation induced squamous carcinoma on unpigmented areas,
hemangiomas and hemangiosarcomas in beagles.
x-rays and radioactive isotopes(beta & gamma emitters) can cause experimental neoplasm's in dog & cat.
chronic irritation, repeated trauma or trauma with concurrent tumor stimulating factors result in
Canine & feline osteosarcomas and fibrosarcomas may be associated with fractures & internal fixation of bones.
Mammary tumors occur frequently in caudal mammary glands & may be associated with repeated trauma to more pendulous glands.
4. parasites :-
spirocerca lupi cause tumors in esophagus(66% osteosarcomas & 34% fibrosarcomas),stomach & aorta in dogs.
liver fluke clonorchis sinensis cause bile duct carcinomas in dogs & cats.
Schistosoma hematobium cause urinary bladder cancer in man
5. Transplantation :-
canine transmissible venereal tumor(CTVT) is the only tumor passed by intact cells from dog to dog
without aid of viral or carcinogenic factors.
Transmitted by coitus & lesions seen on penis & vagina.
Orogenital contact allows cellular implantation in oral cavity & nose.
6. Congenital origin :-
Embryonal nephromas may be detected in puppies less than 6 months of age & occurs due to abnormality in embryogenesis.
7. carcinogens :-
Tonsillar squamous cell carcinoma & malignant mesothelioma are more common in dogs of urban areas exposed to industrial chemical wastes like asbestos.
Tumor cell growth
Growing acceptance that tumors arise from mutation of a single cell k/as stem cell.
Sequential selection of further mutant subpopulations may occur showing genetic variability, allowing advanced malignancies to have highly individualistic karyotypes & biological behaviour.
Leading to variability to treatment response b/w patients or within treatment course of a single patient.
Tumors of clinically detectable size represent late stages of malignant growth.
How they invade & metastasize ?
Invasion is the intrusion on & destruction of adjacent tissues.
Metastasis is spread to other locations via blood or lymph.
Local invasion & metastasis are best clinical criteria of malignancy available.
Invasion without metastasis is found in many tumor types in dogs & cats e.g. adrenal cortex carcinoma, thyroid carcinomas, hepatomas etc.
Metastasis depends upon; cohesiveness of the cells, rate of tumor growth, degree of necrosis & amount of connective tissue surrounding the tumor.
Malignant melanomas & osteogenic carcinomas have high metastatic rate.
Tumor metastasis involves following steps ;-
Invasion of cells from primary tumor into surrounding tissue including blood vessels & lymph vessels.
Release of embolic tumor cells into the circulation.
Arrest of emboli in capillary beds of distant organs.
Invasion of cells from embolic focus, infiltration into surrounding tissue & multiplication and
Tumor Invasion occurs by ;
Increased pressure & destruction of host stroma.
Decreased cohesiveness of neoplastic cells.
Increased mobility of cells.
Formation & secretion of high levels of proteolytic enzymes that disrupt host stroma & facilitate invasion.
Local inflammation caused by actively growing tumors attract leukocytes by chemotaxis containing large amount of proteolytic enzymes.
After invasion has occurred tumors may metastasize by;
Direct extension / infiltration in adjacent organs.
Transplantation/transcoelomic migration into body cavities by seeding of exfoliated cells from primary tumor to serosal surface of abdomen or migration around blood vessels passing through diaphragm allowing implantation in pleural cavity.
Lymphatic system- by permeation or embolism most common method in many carcinomas.
Hematogenous route- by invasion into thin walled veins. Arteries relatively resistant. Lungs are most preferred sites for hematogenous
metastasis since they receive & filter all the venous blood before returning it to heart, followed by liver.
e) Implantation- by
Natural passage- tumor cells growing on surface of hollow organs may cast into lumen & may be implanted in other areas e.g. cells from renal pelvis carcinoma may be washed down to bladder & implanted there. Likewise tumors of bronchi & bowel may be implanted in other parts of bronchial tree & bowel respectively.
Inoculation- it’s a rare hazard in surgery where neoplastic cells are implanted on edges of a wound which develops into a new tumor.
coitus - like the venereal tumors in dog.
Clinical staging determines extent of disease in living animals which serves following purposes;
Groups of animals may be matched for study.
To plan treatment.
Accurate prognostic criteria based on clinical presentation may become available.
Extent of disease becomes known to avoid inappropriate therapy.
Differentiates local disease( surgery, radiation, cryotherapy) from systemic disease(chemotherapy, immunotherapy).
In veterinary medicine standard for clinical staging is the TNM system ( T =tumor size; N =regional lymph node; M =distant metastasis) developed through WHO.
TNM classification made after histological, cytological, radiographic and physical examination.
Size of primary tumor designated from T0 to T4.
N0 suggests no regional lymph node involvement & N1 that regional lymph nodes are positive for metastatic disease.
Normal lymph nodes are freely movable & usually not palpable while tumor invaded lymph nodes become enlarged, firm, & sometimes fixed.
Enlarged , soft nodes may be reactive to tumor inflam, superficial infection, or antigenic stimulation.
This dilemma can be solved by cytological examination of fine needle aspirates of all enlarged lymph nodes.
Distant metastasis is described by the terms M0 or M1.
Finally on the basis of TNM classification, tumors are assigned a “clinical stage” designated from 1 to 4.
Clinical stage-1 :- local disease with no metastasis.
Clinical stage 2, 3, & 4 designate degrees of metastasis & stage 4 being most severe.
Diagnosis of cancer
clinical - any rapidly growing tumor bleeding profusely & does not heal must arouse suspicion of cancer.
Biopsy - cytological exam. Of tumor aspirate may reveal anaplasia, invasion & loss of polarity in malignancy. Most reliable method.
Radiology -possible in viscera & bone.
Exfoliative cytology _ cancer cells cling together less firmly than normal cells & those at surface when cast off (exfoliate) can be collected, stained and diagnosed. Used in humans for uterine & bronchiogenic cancer. first used by Papanicolou so named as PAPA’s test.
e) Chemical & serological tests - in humans enzyme estimation in some cases of prostrate cancer and bone sarcoma is useful… no such test avail. in animal medicine.
What are their Effects on host ?
1. Pressure atrophy of surrounding organs.
2. Obstruction of hollow organs.
3. Exudate in serous cavities bcoz of inflammatory response of cell deposits on serous membranes e.g. malignant ascites.
4. Destruction of tissues, blood vessels & nerves.
5. Infection- due to ulcerated surface tumors.
6. Malignant cachexia- due to competition for essential nutrients & release of some catabolic products like lactic acid injuring host cells. Affection of GIT causes starvation & emaciation.
7. Anemia due to malnutrition, recurrent hemorrhages, marrow depression(long standing infections, secondary tumors causing atrophy of marrow)
8 . Paraneoplastic effects – any effect not caused directly by the tumor or its metastasis & includes topic hormone production by cells of endocrine tumors, ectopic hormone ( by derepression of genes) production by cells of non-endocrine tumors & production of various biochemical substances by cancer cells.
Parathyroid hormone……………………osteoporosis, big head in horses.
Sertoli cells…………………………………… feminization of males.
Non-endocrine tissues produce ectopic hormones, hormone precursors, prostaglandins, immunoglobulin's, enzymes, immune complexes, antigens that provoke immune response, block receptors.
Paraneoplastic effects ;-
first indication of neoplasia.
allow early diagnosis.
can be used as a marker for tumor recurrence or to monitor response to therapy.
may be more debilitating or immediately life threatening than tumor from which it arose.
9 . Death :- malignant neoplasm ultimately produces death of host.
Monoclonal antibody therapy.
Role of surgery
Surgery as immunotherapy.
Definitive procedures- surgery as a sole curative procedure in tumors localized to a nonvital organ or region & amenable to total removal e.g. tumors of skin, mammary gland & genitilia.
Certain surgical procedures prevent formation of neoplasm's like ovariohysterectomy in bitch before 2 years of age decreases frequency of mammary neoplasm's.
Palliative procedures- to increase life of a patient through local reduction of tumor mass in spite of local invasion or metastasis e.g. repeated removal of fibrosarcomas recurring locally ameliorate the clinical signs & allow animal to live a fairly comfortable life for several months to years.
Amputation of limb with osteosarcoma may also be included in this.
Exploratory procedures- in establishing diagnosis & prognosis like exploratory celiotomy, or thoracotomy to confirm or rule out a suspicion of neoplasia based on history, physical exam, laboratory data, & radiographs.
Combination therapies- surgeon becomes a member of multidisciplinary team that includes immunologists, radiologists, pathologists, pharmacologists & biochemists in decreasing the tumor load.
surgical removal increases immunocompetence.
Residual microfoci of tumor cells more sensitive to chemotherapy & immunotherapy than primary tumor bcoz metastasis have a better blood supply & more rapid rate of cell turnover.
Surgery as immunotherapy- neoplasm's limit the hosts immune system by producing specific & nonspecific immunosupression of cancer patient by constantly shedding soluble tumor associated antigens into blood which circulate alone or as Ag-Ab complexes & inhibit lymphocyte mediated destruction of tumor cells.
Also cause nonspecific generalized immunosupression of patient.
Immunosupression correlates with the stage of disease & size of tumor burden.
Surgical maneuver lowers tumor mass & reverses both specific & nonspecific immunosupression increasing
immunocompetence of patient thus acting as one form of immunotherapy.
Older patient with other systemic & metabolic disorders not suitable.
Biological behavior, location & extent of tumor.
Careful evaluation of regional lymph nodes for evidence of metastasis.
Radiography of regional bones & thoracic cavity to rule out metastasis.
Tumor type, presence or absence of metastatic disease, location of neoplasm, appearance & function of animal after surgery, owner considerations including cost & clients emotional wellbeing and wishes.
Clinical staging of neoplasm.
Anesthesia in cancer patient essentially same as that for any aged or debilitated patient.
Regional or epidural anesthesia recommended.
Local anesthesia potentiates metastasis.
General anesthesia aggravates immunosupression.
prep of wide area for surgery with strict aseptic technique as cancer patients are already immunosuppressed to decrease chances of dev. of infection.
Larger incision is given for removal of tumor with minimal manipulation & trauma.
Minimal & gentle handling of neoplastic tissue to prevent exfoliation of tumor cells into wound & systemic circulation.
Ligation of venous vascular supply of tumor early in surgical procedure minimize exfoliation & circulation of tumor cells.
Flushing of surgical site with sterile phy.saline may wash away exfoliated cells & prevent recurrence.
Flushing of body cavities controversial.
Wide margin of normal tissue must be excised to ensure total removal of the neoplasm's. Margin of at least 1cm suffice.
Wound left open to heal by granulation tissue or to perform reconstructive procedures. .
En bloc resections i.e. removal of the primary tumor, intervening lymphatic's, and regional lymph node in continuity are recommended if these are also affected through the single incision.
Many tumors removed by routine surgical technique without any specific PO management.
Administration of antibiotics.
Medical management like insulin therapy after surgical resection of pancreatic B-cell adenocarcinoma, thyroid hormone therapy in thyroid neoplasm's, calcium supplementation in parathyroid neoplasm's.
Special diets & stool softeners indicated in various gastrointestinal-colonic resections.
Administration of ionizing radiation & its absorption by normal or neoplastic tissue.
Therapeutic forms of ionizing radiation include x-rays, gamma rays, electrons, neutrons & other charged particles that deposit their energy in randomly in tissues.
Deposited energy greater than chemical binding energies of molecules within tissues.
Ionization of molecules removes orbital electrons which lead to chemical changes in vicinity of ionization causing damage biologically important intracellular molecules.
Mechanism of radiation therapy ;-
Direct intraction with molecules & removal of their orbital electrons and changes chemical configuration of molecule & damage cells.
DNA being most susceptible.
Indirect mech.:- radiations produce free radicals e.g. peroxides, OH¯ ,HO2 & H2O2 which are highly unstable producing crucial changes within cells.
Methods of radiation therapy:-
1. Teletherapy;- radiation source kept at a distance from lesion.
Superficial x-ray therap y- energy of x-rays in range of 60-100 KeV.
Deep x-ray therapy- energy of x-ray 200-300KeV.
Super voltage therapy- by x-ray machines provided with linear accelerators or cyclotrons, or via isotopic x-ray machines with cobalt or cesium in a sealed form.
Particulate beam therapy- by electrons, protons or neutrons.
2. Brachytherapy: - use of radioisotopes either within interstisium or on surface of a neoplasm.
Radioisotopes in forms of seeds, grains, needles or surface applicators.
Interstitial brachytherapy- ¹⁹⁸Au, ⁶⁰Co etc.
Pliesotherapy( surface brachytherapy)- ⁹⁰Sr.
Systemic brachytherapy- ¹³¹ I and ³²P.
Principles of radiation therapy
RT done in multiple treatments given over a period of time- fractioned therapy.
10-12 fractions of 4-5 Gy each time usually 3 times per week.
Purpose is to use varied characteristics of normal & neoplastic cells.
4 factors called as 4R’s of radiation therapy are used to design radiotherapy protocol which are Reoxygenation, Repair , Repopulation, & redistribution.
Cesium grains used in interstitial brachytherapy
Teletherapy in a human patient
An Indian rhino being treated for skin tumor beneath horn by surface brachytherapy
Teletherapy of a dog
Use of any or all components of hosts immune system to control, damage, or destroy malignant cells.
Interest in IT appeared after demonstration of tumor specific antigen in chemically induced neoplasms in mice so was assumed that similar antigens would be found in spontaneous tumors in man & animals.
Evidence of significace of immune system on tumor behavior ;-
Increased incidence of tumors in congenitally immunosuppressed humans or animals.
Demonstration of blocking factors(Ag-Ab complexes )
inhibiting lymphocytes invitro.
Spontaneous regression of of tumors.
Regression of metastasis after resection of primary tumor.
Failure of circulating tumor cells to metastasis in some cases.
Infiltration of tumor by mononuclear cells.
Increased tumor incidence with age.
Evasion of immune response by tumors ;-
Tumors in privileged sites.
Overwhelming the immune system.
Techniques of IT
Active specific immunotherapy by tumor vaccines prepared from TSA or modified or killed preparations of whole cells.
Passive immunotherapy by administration of immune sera, immune lymphocytes, specific antibodies, complement, immune RNA preparations & monoclonal antibodies.
Non-specific immunotherapy by biological modulators like MBV,BCG, corynebacterium parvum & c .granulosum, vaccinia virus, freunds adjuvent. Chemical immunostumilators like levamisol, DNCB, MDP, azimexon & tuftsin.
Alkylating agents e.g.; cyclophosphamide,
Anti-metabolites e.g.; methotrexate
Plant alkaloids e.g.: vincristine
Antibiotics e.g.; actinomycin-d
Hormones e.g.: prednisolone
Miscellaneous agents e.g.: L-asparaginase
Cancer drug injection
Surgical use of freezing temperatures
Desired effect is tissue necrosis that result from freezing
Cell death from freezing is direct result of ice crystal formation, intracellular fluid and electrolyte disturbances, denaturation of cell membranes and thermal shock.
Vascular stasis in frozen tissue due to thrombosis and infarction are indirect effects
Freon -60 ̊c
Dry ice -78 ̊c
N2O -89 ̊C
used as spray or with probes.
Temp. above 41 ̊c are cytotoxic.
Degree of cell killing depending on temperature & duration of heating.
Increase in heating time- rate of
killing is exponential.
Hyperthermia is a specialized therapy that involves heating selected tumors to 106 to 108 ̊F for up to one hour. Hyperthermia can be delivered in combination with radiotherapy .Cancers most commonly treated with hyperthermia are head and neck, prostate, cervical, skin soft tissue sarcoma, and chest wall recurrences of breast cancer.
How Hyperthermia Works
Certain cancer cells can become resistant to cancer treatment when they become oxygen-starved due to poor blood supply. Heat application causes increased blood flow and oxygen to the tumor making the cancer cells more susceptible to cell death. Hyperthermia is always preceded or followed by radiation or chemotherapy because it enhances the effectiveness of these treatments.
What to Expect
Hyperthermia can be delivered externally or internally. An external device, similar to a heating pad, is used for tumors close to the skin’s surface. For all others, small wires are inserted into surgically implanted hollow tubes and energized with microwaves to heat the tumor. The implanted tubes are removed when all treatments are complete.
Benefits of Hyperthermia
Consistent results for many decades.
Improves survival in recurrent or hard-to-treat cancers.
Virtually painless procedure.
Makes cancer cells vulnerable while preserving surrounding healthy tissue
Cancers Treated with Hyperthermia
Head & Neck Cancer
Type of Hyperthermia
local hyperthermia :- Treatment area includes a tumor or other small area.
Heat is applied from the outside with high-frequency waves aimed at the tumor.
Inside the body a small area may be heated with thin heated wire probes, hollow tubes filled with warm water, or implanted microwave antennae and radiofrequency electrodes.
2. Regional hyperthermia:- An organ or a limb is treated.
Magnets and devices that produce high energy are placed over the region to be heated.
or Some of the patient's blood is removed, heated, and then pumped into the region to be heated. The process is called perfusion.
3. whole body hyperthermia:-
The whole body is treated when cancer has spread.
warm water blankets.
Inductive coils (similar to the coils in an electric blanket). Thermal room or chambers
Are there any side effects?
There are no known complications of hyperthermia. Side effects may include skin discomfort or local pain. Hyperthermia can also cause blisters and occasionally burns but generally these heal quickly.
The term LASER stands for "Light Amplification by the Stimulated Emission of Radiation." Laser light is concentrated so that it makes a very powerful and precise tool. Laser therapy uses light to treat cancer cells.
The following are some of the different types of laser used for cancer treatment: