FACULTY OF MEDICINE AND HEALTH SCIENCES

SCHOOL OF PHARMACY

Name: NDARIMANI INNOCENT GEORGE

Registration number: R212649G

Program: BSc HONOURS DRUG DISCOVERY AND

THERAPEUTICS

Program code: HPST 2.1

Course Name: CLINICAL BIOCHEMISTRY PCH201

An account of Cancer Pathologies
Give an account of cancer pathologies, outlining the diagnosis, treatment and its
management. (50)
Cancer is the common name for all malignant tumors. The term tumor was originally applied to the
swelling caused by inflammation, but by long precedent, the term is now equated to neoplasm.
According to the National Library of Medicine, a neoplasm is an abnormal mass of tissue growth
which exceeds and is uncoordinated with that of the normal tissue and persists in the same excessive
manner after cessation of the stimuli which evoked the change that is the cancer cells have developed
mechanisms to evade apoptosis, continuing to grow and divide. Cancer cells can also break away from
the tumor and enter the bloodstream or the lymphatic system to invade other tissues, spreading in a
process called metastasis. There are 4 common types of cancers which are carcinomas, sarcomas,
lymphomas and leukemia. Cancers have many etiologies, from predisposing factors such as age,
heredity, environmental exposure to acquired pre-cancerous diseases such as leukoplakia.

Carcinomas are the most common type of cancers, beginning in the epithelial cells of tissues. Lung
cancers are good example of carcinomas and also are the most insidious and aggressive neoplasms
(Rajdev, et al., 2018). Smoking is the greatest risk factor of lung cancers (Groot, et al., 2018). The risk
correlates also with family history of lung cancer (inherited defective genes). Other carcinogens for
lung cancers are radon, asbestos, arsenic, vinyl chloride and polycyclics aromatic hydrocarbons
(PAHs). The 4 major histologic types of lung cancers, also referred to as bronchogenic carcinomas, are
squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma.

Adenocarcinoma is the most prevalent non-small cell lung carcinoma (Myers & Wallen, 2022) with
glandular differentiation that develops in the periphery of the lungs, which can grow in various
patterns including acinus, papillary, brochioalviolar and solid with mixed tumor. It is common in non-
smokers and women. It has a moderate rate of growth and metastasis occurs early to hilar nodes, chest
walls and mediastinum, brain, bone and liver. Its clinical features include dyspnea, weight loss, chest
pain, cough and hemoptypsis. Adenocarcinoma can be identified by routine chest radiograph/ CT scan.
It can be treated by surgical resection and chemotherapy and radiation therapy to decrease the risk of
recurrence.

Squamous cell carcinoma is also another type of non-small lung cancer which has a slow rate of
growth and has late metastasis mainly to hilar lymph nodes, chest wall and mediastinum. It is most
common in men. It typically develops in segmental bronchi, causing bronchial obstruction and regional
lymph involvement. Pancoast Tumor, or pulmonary sulcus tumor, begins in the upper portion of the
lung and commonly spreads to the ribs and spine causing classic shoulder pain that radiates down the
ulnar nerve distribution. Signs and symptoms of squamous cell carcinoma include airways obstruction,
nonproductive cough, sputum production. It can be diagnosed through biopsy, sputum analysis,
immunohistochemistry, electron microscopy and bronchoscopy. Chemotherapy & radiotherapy can be
done to prevent metastasis of the cancer cells.
Large cell carcinoma is a merely descriptive term indicating a subtype of lung cancer with no specific
features of small-cell lung cancer, adenocarcinoma or squamous cell carcinoma (Pelosi, et al., 2015).
Large cell carcinoma has a fast rate of growth and has early, extensive metastasis in the thoracic
structure, brain, bone and adrenal glands. Its signs and symptoms include cough, hemoptysis, chest
wall pain, pleural effusion, sputum production and pneumonia- induced airway obstruction. The
diagnosis involves bronchoscopy, sputum analysis and electron microscopy. Treatment again is
surgical resection (limited because of the often aggressive course of this tumor type) and
chemotherapy and radiation therapy (palliative role to minimize symptoms of advanced disease).

Oat cell carcinoma (small cell lung cancer) is most aggressive type and has greater tendency to
metastasize than non-small cell lung cancers. It can be diagnosed through bronchoscopy, biopsy,
sputum analysis and electron microscopy. It is strongly related to cigarette smoking and commonly
occurs within the mainstem bronchi and segmental bronchi, majority cases having hilar and
mediastinal involvement. Symptoms of oat cell carcinoma include paraneoplastic syndrome,
hyponatremia, fluid retention and fatigue. Surgery is rarely indicated even in those with limited stage
disease because of the need for immediate systemic therapy. Chemotherapy and radiation therapy
offers the best hope for prolonged survival and quality of life. Etoposide, an inhibitor of topoisomerase
II, is used to treat small cell carcinoma of the lungs in combination with cisplatin. Prevention of
individuals from smoking and promotion of smoking cessation can have high impact managing this
type of cancer. Pharmacotherapy has been shown to be effective without counseling; however,
combining pharmacotherapy with behavioral counseling leads to the highest quit rates (The Clinical
Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff,
2008)

Leukemia, a cancer of white blood cells, is most common in children. It can be myeloid or
lymphocytic depending on which bone marrow cells starts in. A single line of myeloid cells in the
bone marrow proliferate abnormally, causing a large increase in the number of non-lymphoid white
blood cells. It can be diagnosed through blood tests or bone marrow test and lumbar puncture. The
development of acute lymphoblastic leukemia requires a hematopoietic stem cell or one of its
committed progenitors to elude the normal mechanisms of homeostatic control that regulate growth-
factor signaling, differentiation, apoptosis, and self-renewal. Common pathway targeted by
translocation-generated chimeric transcription factors, such as mixed –lineage leukemia (MLL) fusion
protein is the HOX gene mediated transcriptional cascade. The MLL protein is required to maintain
this transcription, whereas members of the polycomb group (PcG) family of proteins repress HOX
gene transcription. HOX proteins, in turn, collaborate with cofactors, including the PBX1 protein, to
induce the transcription of downstream target genes, whose products influence self-renewal,
proliferation, and differentiation of hematopoietic stem cells and their committed progenitors proteins.
Acute lymphoblastic leukemia usually starts slowly and then rapidly become as the number of
immature white blood cells in blood increase. Its symptoms involve pale skin, tiredness, and repeated
infections over a short time and sudden temperature increases. Leukemia can be treated in different
separate phases which are indication, consolidation, maintenance therapy and preventive treatment to
spinal chord. These treatments may include chemotherapy, target therapy, radiation therapy and bone
marrow transplant. Aminopterin and amethopterin, analogues of folic acid, competitively inhibit
dihydrofolate reductase and block the formation of THF. The biosynthesis of purines, thymine
nucleotides and hence DNA is impaired. This results in the blockage of cell proliferation. Aminopterin
and amethopterin are successfully used in the treatment of many cancers, including leukemia.

Another example of cancer pathology is lymphoma. The malignant lymphomas, including both
Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), represent a diverse group of diseases
that arise from a clonal proliferation of lymphocytes. There are more than 30 unique types of
lymphoma with distinct history giving rise to marked differences among these lymphomas (Matasar &
Zelenetz, 2008). Hodgkin lymphoma is a cancer that develop from abnormal B-cells, causing enlarged
lymph nodes without pain in the neck. Other symptoms may include drenching or frequent sweats
especially at night, weight loss, tiredness and persistent itch all over the body. HIV infections are risk
factors for developing Hodgkin lymphoma. It is staged into four stages using ann arbor staging system
with stage 1 being the early stages and stage for the late stage. The diagnosis of HL requires
demonstration of Reed Sternberg (RS) cells in biopsy. The RS cells are multinucleated giant cells with
a clear halo around prominent nucleoli which are scattered in a background rich in lymphocytes,
histiocytes, eosinophils and plasma cells effacing the normal lymphoid architecture. Chest X-rays and
CT scan of thorax, abdomen and pelvis are other possible ways of diagnosis. Possible treatments for
HL include radiotherapy, chemotherapy and combined modality therapy. High dose chemotherapy
with stem cell support is extensively used in patients with relapsed and refractory HL.

The other type of cancer pathologies are sarcomas, cancers of connective tissue. Sarcomas are a
diverse group of rare tumors, accounting for a small percentage of all malignant tumors. They arise
from embryonic mesoderm and present most commonly as an asymptomatic mass originating in an
extremity, but can occur elsewhere in the body (Sinha S, 2010). Various types of sarcomas include
bone sarcomas (osteosarcoma and chondrosarcomas), liposarcomas, peripheral primitive
neuroectodermal tumors and soft tissue sarcomas. Most sarcomas arise de novo with no obvious cause.
Implementation of cytogenetic analysis led to identification of oncogenes and chromosomal
translocations associated with certain histologic subtypes of sarcomas (Ribeiro, et al., 2019). Mutation
in tumor suppressor genes like Rb gene or P53 gene are associated with development of sarcoma of
soft tissue and bone.

Osteosarcoma occurs mainly in the metaphysic of the long bones. The etiology is unknown.
Predisposing factors include, age- (10-25), gender-(male), family history, teenage growth spurt, tall for
age, previous treatment with radiation, benign & non-cancerous bone tumor, lack of exercise, and
DNA mutation. DNA mutation activates the oncogene which leads to a deactivation of the suppressor
gene which causes a malignant osteoblast that leads to proliferation of abnormal osteoblasts.
Symptoms include bone pain, warm lump, swelling and redness at the site of tumor and unexplained
fever. The diagnosis in suspected patients include X-ray, CT and MRI scan, Bone scan, ET scan,
biopsy and also blood test. A various combination of treatment approaches including radiotherapy and
chemotherapy. High-dose methotrexate with citrovorum may be used.

References
Groot, P., Wu, C. C., Carter, B. W. & Munden, R. F., 2018. The epidemiology of lung cancer.
Translational Lung Cance Research, 7(3).

Matasar, M. J. & Zelenetz, A. D., 2008. Overview of lymphoma diagnosis and management. Radiol
Clin North America, 46(2), p. 175.

Myers, D. J. & Wallen, J. M., 2022. Lung Adenocarcinoma. NIH.

Pelosi, G. et al., 2015. Large cell carcinoma of the lung: a tumor in search of an author. A clinically
oriented critical reappraisal. Lung Cancer, pp. 226-231.

Popper, H. H., 2016. Progression and metastasis of lung cancer. Cancer Metastasis Rev, pp. 75-91.

Rajdev, K. et al., 2018. An Unusually Aggressive Large Cell Carcinoma of the Lung: Undiagnosed
until Autopsy.

Ribeiro, P. I., Melo, J. B. & Carreira, I. M., 2019. Cytogenetics and Cytogenomics Evaluation in
Cancer. Int J Mol Sc.

Sinha S, P. A., 2010. Diagnosis and managementof soft tissue sarcoma. BMJ.

Sirica, A. E. et al., 1993. Pathogenesis, in :Concepts in cancer medicine. The Pathobiology of

Neoplasia, pp. 157-164.

The Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons,
and Staff, 2008. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A
U.S. Public Health Service report. American journal of preventive medicine, 35(3), pp. 158-176.