Discuss how to distinguish a benign from a malignant neoplasm. (<250 words)

Both benign and malignant neoplasms represent autonomous monoclonal new growth of cells, and an exact distinction between them is not always possible. However, malignancy is most often characterized by presence of metastases, followed by features such as invasiveness, lack of circumscription, and necrosis or variegation. Cytologic features of malignancy, important in grading, include cellular pleomorphism, increased nuclear/cytoplasmic ratio, presence of mitotic figures or irregular and bizarre mitoses, irregular borders, and nuclear hyperchromatism. More of these features increase the degree of anaplasia, indicating the neoplasm is less differentiated. Malignant neoplasms are more prone to show aneuploidy by DNA analysis and show chromosomal anomalies. Malignant tumors have a shorter doubling time (as low as a few months) because of the increased growth fraction of cells.

Benign neoplasms tend to be grossly discrete, circumscribed, or encapsulated masses. They do not often invade and rarely metastasize. They tend to be well-differentiated and closely mimic the tissue of origin. Thus, they show little anaplasia. They tend to be slow growing with a doubling time of several years, and cause symptomatology from pressure effects on surrounding tissues. Thus, they are more amenable to surgical therapy and have a better prognosis than malignant neoplasms. Benign tumors may often retain the function of the cell of origin. They are uncommonly aneuploid.

Discuss how you would use clinical, laboratory, and pathologic findings to determine what you could tell your patient diagnosed with a neoplasm about the prognosis. (<250 words)

(Example 1)

Neoplasms can be benign or malignant. The most reliable indicators of malignancy are invasion and metastases. By light microscopy, invasion can best be determined by demonstrating that the neoplasm has degraded the basement membrane and infiltrated the underlying stroma. Flow cytometry can be used to determine if aneuploidy or a high S-phase fraction of cells are present, both of which indicate a more aggressive tumor and a worse prognosis. Prognosis can also be affected by the cell type of the neoplasm which can be determined by light microscopy and tumor specific antigen staining. Malignant neoplasms tend to be less differentiated with more cellular pleomorphism, hyperchromatism, mitoses, and higher nuclear/cytoplasmic ratios. Differentiation determines the grading of a neoplasm, usually on a scale from 1 to 3, with a lower grade indicating a better prognosis. Staging of a neoplasm helps determine the prognosis. Staging is divided into Tumor stages 1 to 4 with increasing size, Nodal stages 0 to 2 increasing wtih the number and extent of lymph nodes involved, and Metastatic stages 0 to 2 increasing with greater spread of the tumor. In general, the higher the stage, the worse the prognosis. However, even benign neoplasms may be worse if they compress vital structures or become difficult to resect. Clinically, a history of weight loss and cachexia usually indicate a malignancy and a worse prognosis.

(Example 2)

A physical examination and patient history may suggest whether a neoplasm is benign or malignant. On palpation, a benign neoplasm will generally be well-circumscribed and mobile, whereas a malignant neoplasm is fixed to surrounding structures because of invasiveness. In addition, a patient with a malignancy will often have experienced a significant weight loss. After biopsy of the neoplasm, light microscopy will aid in determination of prognosis through an assessment of differentiation. Benign neoplasms are always well-differentiated, while malignant neoplasms may be well, moderate, or poorly differentiated. A benign neoplasm can usually be removed with surgery alone, but a malignant neoplasm may require further treatment with radiation and/or chemotherapy. Determination of the cell type of the malignant neoplasm is important because different cell types respond differently to therapy. Cell type can be determined by special staining, for example cytokeratins for carcinomas, vimentin for sarcomas, and leukocyte common antigen for lymphomas. Certain neoplasms such as oat cell carcinomas of the lung may also produce hormone-like substaances such as ACTH and lead to appearance of a paraneoplastic syndrome. A higher grade (less differentiation) and a higher stage (greater extent of spread through invasion and metastasis) for a given malignant neoplasm indicate a worse prognosis.

Discuss the causes and consequences of paraneoplastic syndromes (<250 words).

Paraneoplastic syndromes are secondary signs and symptoms produced at sites distant from the neoplasm itself. These syndromes may occur in up to 10 to 15% of malignancies, and they may be the first or most prominent manifestation that the patient suffers, or may help in detection of the malignancy by laboratory testing for a substance secreted by the neoplasm. The cause of the paraneoplastic syndrome may be due to the production and release of physiologically active substances, or it may be idiopathic. Examples of paraneoplastic syndromes include renal cell carcinomas that produce erythropoietin and lead to an increase in circulating RBC's. Another common syndrome is that caused by oat cell carcinoma of the lung with production of ectopic ACTH. This causes excessive adrenal release of cortisol and can induce Cushing's syndrome with a characteristic "moon facies", truncal obesity, and hypertension. Pulmonary squamous cell carcinomas, as well as breast and kidney neoplasms, have been known to produce parathormone-like substances which induce the loss of bone mass and cause hypercalcemia. Subsequent metastatic calcification can then occur. The carcinoid syndrome is a paraneoplastic phenomenon caused by neoplasms of the neuroendocrine cells, often in the gastrointestinal tract. They may produce substances that lead to flushing, nausea, vomiting, and enhanced intestinal motility with diarrhea. Less well understood syndromes include hypoglycemia with production of insulin-like substances, Trousseau's syndrome with vascular thrombosis, and acanthosis nigricans of the skin.

Discuss how you would diagnose a neoplasm in your patient and then determine the prognosis. (<250 words)

(Example 1)

A complete history and physical examination can suggest neoplasia. Persons with a family history of malignancies, such as breast or colon, may be at increased risk. Finding a lump or nodule on physical examination can suggest that a tumor is present. Slow growing nodules that are well defined and not fixed to surrounding tissues are more likely to be benign. Larger masses that have been noted to be increasing in size and have ill-defined borders are more likely to be malignant. However, in order to determine if the mass is benign or malignant, a sample of the tissue or cells from the lesion must be obtained. This can be done by methods such as Pap smears, sputum collection, fine needle aspiration, biopsy, or resection of the suspected neoplasm. Examination of the cells via light microscopy will indicate if the neoplasm is benign or malignant. Benign neoplasms resemble the cell of origin, do not invade, and do not metastasize. Malignant cells are usually pleomorphic, have a high nuclear/cytoplasmic ratio, and have mitoses that can be abnormal. Malignancies are graded from well-differentiated to poorly differentiated and are staged by the TNM system. Tumors that are larger have a higher T stage; those that involve lymph nodes have an N score depending upon location and number involved; evidence for metastatic spread by physical examination or radiographic procedures results in an M1 score. In general, malignancies with a higher grade and stage have a worse prognosis.

(Example 2)

There are many screening tools to determine if a neoplasm is present and if it might be malignant. Benign neoplasms are localized and have a good prognosis, unless they are located in a place such as the cranial cavity that makes them more difficult to remove. Biochemical markers can be utilized to suggest a malignancy. For example, the prostate specific antigen can be elevated in persons with prostate cancer. Some malignancies may be found by the presence of a paraneoplastic syndrome with an endocrine effect. For example, the ACTH is elevated in persons with Cushing syndrome that can occur with some lung cancers. Screening tools can consist of radiographic procedures such as chest radiographs to find lung cancers and mammography to find breast cancer. Screening can include procedures such as colonoscopy to find colon cancers and bronchoscopy to find lung cancers. Looking for occult blood in the stool is a good way to find colon cancers. Once a tumor is found, it must be sampled and viewed under the microscope to determine if it is benign or malignant. Benign tumors usually have a good prognosis because they are localized and do not invade or metastasize. Malignant tumors must be graded and staged. Grading determines how well the tumor resembles the cell of origin; staging determines how far it has spread. In addition, other techniques such as immunostaining with cytokeratin for carcinomas and vimentin for sarcomas can help determine the origin of the tumor.