Neoplasia

By
Prof. J.T. Anim
Department of Pathology
Lecture V
Topics
 Effect of neoplasm on host
 Effect of host on neoplasm
 Tumour immunity
 Spontaneous regression of malignant
tumours
Effect of Neoplasm on Host
 Local effects
 Mechanical pressure
 Destruction of tissue (pressure/aggressive invasion)
 Haemorrhage +/- ulceration
 Infection
 Systemic effects
 Fever - TNFα, IL-1 (tumour cells, macrophages)
 Cachexia (anorexia, malabsorption, anaerobic metabolism
of neoplasm, cytokines eg. TNFα = cachexin, IL-6)
 Effect on immune system (immunosuppression due to
tumour itself or treatment; autoimmunity – non-organ
specific)
Effect of Neoplasm on Host
 Systemic effects Contd.
 Haematological effects
 Anaemia – iron deficiency, nutritional, excess Rbc
destruction (AIHA)(HD, lymphomas, thymoma), MAHA (ca
stomach, pancreas, colon, lung, breast), decreased
erythropoietin, sideroblastic, red cell aplasia (thymoma)
 Increased red cell production – ectopic EPO (renal cell
carcinoma, cerebellar haemangioblastoma, uterine
fibroleiomyoma, liver carcinoma, ovarian carcinoma, lung
carcinoma)
 Effects on platelets and clotting – thrombocytopaenia
(immune-mediated destruction); intravascular coagulation
(prostate, bronchus, stomach, breast), migratory
thrombophlebitis (carcinoma of bronchus, pancreas,
stomach, female genitalia, breast – mucin producing
tumours)
Effect of Neoplasm on Host
 Systemic effects contd
 Cutaneous manifestations
 Acanthosis nigricans – 75% adenocarcinoma
 Dermatomyositis – 15% malignancy
 Exfoliative dermatitis – lymphomas & leukaemias
 Erythema gyratum repens – carcinoma of bronchus
 Pigmentation – carcinomatosis
 Pruritis – lymphomas & some carcinomas
 Herpes zoster – Hodgkin’s and other lymphomas
 Acquired ichthyosis – lymphomas
 Necrolytic migratory erythema - glucagonoma
Effect of Neoplasm on Host
 Neuromuscular effects
 Myopathy – carcinomas & lymphomas
 Myasthenic syndrome – oat cell carcinoma of bronchus,
thymoma
 Mixed neuropathy (sensory and motor)
 Ca bronchus, stomach, breast, lymphoma, myeloma
 Sensory neuropathy – carcinoma of bronchus
 Autonomic neuropathy
 Dementia or psychosis
 Cerebellar degeneration – ca bronchus, ovary, lymphoma
 Brain stem degeneration
 PMLE (papova virus) – rarely, lymphoma
Effect of Neoplasm on Host
 Systemic effects contd
 Endocrine effects
 Appropriate hormone production
 Ectopic/inappropriate hormone production

 Non-metastatic osseous and soft tissue

changes (clubbing)
Effect of Neoplasm on Host
 Inappropriate hormone production by tumour
cells
 Cushing’s syndrome (ACTH production)
 Oat cell carcinoma of bronchus
 Thymoma
 Carcinoid tumours
 Medullary carcinoma of thyroid
 Hyponatremia (ADH-like substance)
 Oat cell carcinoma of bronchus
 Hypoglycaemia (insulin-like substance)
 Mesothelioma
 Liver cell carcinoma
 Adrenal cortical carcinoma
Effect of Neoplasm on Host
 Inappropriate hormone production by tumour cells
 Hypercalcaemia (prostaglandins, parathormone)
 Squamous cell carcinoma of bronchus, cervix
 Renal cell carcinoma
 Lymphomas
 Breast carcinoma
 Polycythaemia (haemopoietin production)
 Renal carcionma
 Uterine leiomyoma
 Liver carcinoma
 Cerebellar haemangioblastoma
 Nephroblastoma (Wilm’s tumour)
 Carcinoid syndrome (5 H-T)
 Oat cell carcinoma of bronchus
 Medullary carcinoma of thyroid
Effect of Neoplasm on Host
 Inappropriate hormone production by tumour
cells
 Gynaecomastia (HCG or human placental lactogen)
 Anaplastic/squamous cell carcinoma of bronchus
 Testicular tumours
 Hepatocellular carcinoma
 Hypertension (excess renin production)
 Nephroblastoma
 Hyperthyroidism (TSH-like substance)
 Hydatidiform mole, choriocarcinoma
 Orchioblastoma
 Malignant teratoma of testis
 Pigmentation (melanin stimulating hormone - MSH)
 Oat cell carcinoma of bronchus
Effect of Host on Neoplasm
 Mainly through interaction with host immune system
 Tumour regression – neuroblastoma, malignant
melanoma, regression of metastases after removal
of primary
 Evidence of immunological reaction
 Histology – infiltration by lymphocytes, plasma cells,
macrophages (correlation with prognosis), granulomas in
draining lymph nodes
 Immune deficiency states and malignancy – Ataxia
telangiectasia, Wiskott-Aldrich, Chediak-Higashi and
Iatrogenic immunosuppression – lymphomas. ?Provides
indirect evidence for cancer immunosurveillance.
Effect of Host on Neoplasm
 Evidence of immunological reaction contd.
 Rejection of tumour by animal hosts (animal
models show CMI controls tumour growth)
 Tumour associated transplantation antigens
(separate from histocompatibility antigens)
 Especially irradiation and chemical-induced tumours
 Virally induced tumours produce TATAs – different
from viral structural proteins
 Spontaneous tumours (animal/human) – less antigens
 Some neoplasms elicit CMI eg. malignant melanoma,
renal carcinoma, astrocytoma
Possible mechanisms
of immune tumour
cytotoxicity in animal
models
Spontaneous Regression
 Shrinkage of a neoplasm that may or
may not lead to total disappearance.
 May be temporary
 May occur without therapy - spontaneous
 Has been observed in medical practice
and in laboratory
Spontaneous Regression
 Series of 176 regressions published
between 1900 and 1966
 Renal cell carcinoma, neuroblastoma,
melanoma, choriocarcinoma, carcinoma of
bladder
 In 41 cases metastases regressed after
resection of primary tumour
Spontaneous Regression
 Neuroblastoma in infants – can
change from malignant to benign
 Neuroblastoma - ganglioneuroma
 Melanoma – regression suggests an
immunological mechanism
 Haemangiomas – spontaneous
regression