What you should know about the clinical implications of tumor

Introduction

The clinical implications of tumor cells may range from minute to large depending on their stages. Signs and symptoms may also reflect the primary anatomical sites involved, including adjacent locations as well.

Before we dive into the clinical implications, let’s discuss the routes of cancer spread & tumor immunity.

Cancers may spread through these pathways: hematogenous; lymphogenous & body cavities.

Hematogenous spread

This is usually common among sarcomas; however, it may involve carcinomas. Here, cancer cells spread to distant sites through arterial or venous cavities. Liver metastasis occurs when primary malignant tumors spread through portal vein. Lung metastasis also happens when primary malignant tumors spread through superior or inferior vena cava.

Lymphogenous spread

Spread through lymphatic vessels is usually common among carcinomas than sarcomas. Metastasis occurs along lymphatic drainage to corresponding lymph nodes. Breast carcinoma involving upper outer and inner quadrants of breast, metastasize to axillary and parasternal lymph nodes respectively.

Lung carcinoma metastasizes to the hilar lymph nodes, and then to the mediastinal lymph nodes. In order to determine the extent spread of primary tumors, a surgeon does an excision lymph node biopsy. A sentinel lymph node is the first regional lymph node draining a lymph flow from a primary tumor.

Enlargement of the lymph node usually indicates lymph node metastasis; however, this may also arise from reactive hyperplasia. In lymphatic hyperplasia, lymphatic cells react against tumor cell debris or antigens.

Infiltration of body cavities and surfaces

This occurs when cancerous cells invade synovial or serous spaces. Here, peritoneal, pericardial, subarachnoid, & joint cavity may be affected. Examples: ovarian carcinoma invading the peritoneal surfaces; gelatinous tumor mass (pseudomyxoma peritonei) within peritoneal cavity, in patients with appendiceal carcinoma.

Tumor Immunity

This refers to the host’s immune reaction against tumor cells. Tumor immunity is mediated by: cytotoxic T lymphocytes (CTLs); NK cell; Macrophage; CTLs provide the major defense against tumor cells.

Tumor cells express two types of non-self-antigens: tumor specific and tumor associated antigens. Genetic mutations arising from proto-oncogenes, tumor suppressor genes, and other gene components of tumor cells produce non-self-antigens. CTLs recognize these non-self- antigens that present on MHC-1 molecule, and hence triggers an immune reaction.  

NK cells which are first line of defense against tumor cells, have NKG2D receptors. These receptors recognize stress-induced antigens on tumor cells. Activating cytokines of NK cells including IL-2 & IL-15, mediate cytotoxic actions on tumor cells.

NK cells also complement the action of CTLs, when MHC-1 molecules fail to express on tumor cells. NK cells and CTLs secrete interferon gamma which activates macrophages. Macrophages engulf and kill tumor cells by producing reactive oxygen species.

Clinical implications of tumor cells

1. Intestinal obstruction (obstructing intussusception)
2. hypopituitarism from pituitary adenoma
3. hypoglycemia, in pancreatic beta-cell adenoma
4. Hematuria and Melena from G.I and urinary tract neoplasms.
5. skin ulcerations from squamous cell carcinoma
6. Cachexia: lean body mass; body fat loss; loss of appetite (anorexia); anemia; weakness.  
7. paraneoplastic syndromes

Cachexia

This is a progressive loss of body fat and protein due to soluble factors (TNF; proteolysis-inducing factor; lipid-mobilizing factor). Cancer cells and macrophages produce TNF which may release fats from adipose tissues that suppresses appetite. Tumor cells secrete proteolysis-inducing factor & lipid-mobilizing factor that break and mobilize protein and fats respectively.

Paraneoplastic syndrome

A symptom complex in cancer patients whose manifestations aren’t just explained by ectopic hormone production by tumor cells, local or distant metastasis. E.g.

1. Cushing syndrome, in small cell lung carcinoma due to excess corticotropin release.
2. Hypercalcemia, in squamous cell carcinoma of the lung and other malignancies including breast, kidney, ovary. This arises from the cancer cell production of parathyroid hormone related protein (PTHRP).
3. polymyopathy, cortical cerebellar degeneration and peripheral neuropathies arising from antibody cross-reaction with neural antigens.
4. Hypertrophic osteoarthrpathy, in lung cancers.
5.  Migratory thrombophlebitis (Trousseau syndrome), in lung and pancreatic cancers.
6.  Acute disseminated intravascular coagulation, In prostatic cancer, and acute promyelocytic leukemia.

Diagnosis of Cancer

In order to know the true causes of our patients’ symptoms and signs, we need to carry out laboratory diagnostic tests. The use of the histology and cytology diagnostic method is common around places. To do this, various sampling methods include: excision biopsy; needle biopsy; fine needle aspiration; cytologic (Pap) smears.

Pap smears identify the individual features of aplastic cells. They are used in screening for cervical cancers.

Grading and staging of cancer

Having a proper laboratory evaluation sets the foundation for accurate grading and staging of cancer.

Grading shows the extent of tumor cell differentiation, and architectural features. It may range from Grade 1 to Grade 4 (well differentiated – undifferentiated).

Staging depends on the size of primary tumor, extent of regional lymph node invasion, & metastasis. This provides the most useful clinical value.

The American Joint Committee on Cancer Staging is a system for staging cancer. This system of classification uses the TNM system. T (Tumor); N (lymph node involvement); M (Metastasis).

T1 to T4 denotes increasing size of primary tumor, T0 means in situ lesion; N1 to N3 means increasing number and range of lymph node involvement, N0 means no lymph node involvement; M1/M2 shows presence of metastases, M0 indicates no metastasis.

Tumor markers

Tumor markers don’t give a conclusive diagnosis for cancers; however, they contribute in the detection of cancers. They are also useful in determining the response to a cancer therapy.  Here are examples you should know:

1. Prostate-specific antigen (PSA) is useful in screening for prostate adenocarcinoma.
2. Carcinoembryonic antigen (CEA) is a useful marker for carcinoma of the colon.
3. Carbohydrate antigen 19-9 (CA-19-9) is a useful marker for pancreatic cancer.
4. Cancer antigen 125 (CA-125) is a marker for ovarian cancer.
5. Cancer antigen 15-3 (CA-15-3) is useful in screening for breast cancer.
6. Immunoglobulin is as well a useful marker for multiple myeloma.