Monster biology qn! n im a chemistry student!!!?

Question

help! its this bio module(e only 1) in my final year and im clueless!!

Decision Brief: You are tasked to lead an epidemiology study to investigate possible

risk factors for neoplasia. Analysis of the data shows that one type of neoplasm is

seen in 2 widely disparate situations: (1) the liver of persons exposed to polyvinyl

chloride and (2) the soft tissue of the arm ipsilateral to a prior radical mastectomy.

The pathology reports about the neoplasms in these 2 groups of patients show a

similar gross appearance – an irregular, infiltrative, soft reddish mass – and a similar microscopic appearance – pleomorphic spindle cells positive for CD31. Discuss how are you doing to arrive at what kind of neoplasm it is and how do you differentiate

from related neoplastic pathologies.

just give me any insight in case u know anyting! god bless u and pls help me!

Answer 1

Hi Zaki,

Here's a few thoughts about how to answer this question.

There's not a lot of info given about the neoplastic cells but it seems as though both patients suffer from angiosarcoma:

an uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels and lining irregular blood-filled spaces. Specialists apply the term angiosarcoma to a wide range of malignant endothelial vascular neoplasms that affect a variety of sites. Angiosarcomas are aggressive and tend to recur locally, spread widely, and have a high rate of lymph node and systemic metastases. The rate of tumor-related death is high.

Basically, these are neoplasms that can occur in many regions of the body and their constituent cells display a range of vascular differentiation, i.e. cells displaying characteristics of blood vessel endothelial cells present in the normal soft tissue in the arm.  And this is also the case for angiosarcoma in the liver.

patient 1. There is evidence to suggest that exposure to vinyl chloride in plastics factories can cause angiosarcoma formation.  There are enzymes in the liver that metabolise vinyl chloride (CYP enzymes). However, some of the metabolites of this reaction are toxic and carcinogenic.

patient 2.  Most likely suffers from LAS (Lymphedema-associated angiosarcoma).  

Lymphedema is a notoriously debilitating progressive condition with no known cure. Lymphedema affects both men and women. In women, it is most prevalent in the upper limbs after breast cancer surgery and lymph node dissection, occurring in the arm on the side of the body in which the surgery is performed. The risk for developing LAS 5 years after mastectomy is approximately 5%.

There's lots of info available on LAS and angiosarcoma in general.  But your question probably focuses more on how to discriminate one type of neoplasm from another rather than requiring a great deal of knowledge about angiosarcoma.

Neoplasms are difficult to diagnose under the microscope for the simple reason that you are trying to identify cells that are, by definition, abnormal.  Usually, the more advanced/aggressive/malignant the tumor, the more heterogeneous the cells will be.

Some things to consider:

1. Despite the abnormal nature of the cells, are there any key markers/traits consistently present on these cells.

  In this case the cells are differentiating into a more vascular phenotype, and vascular endothelial cells have many key markers.  You can target these markers with monoclonal antibodies that are attached to staining/dying agents and then view the sample under the microscope to see if the cells have bound the antibody (i.e. are expressing vascular antigens). This is called immunohistochemistry.

Your question mentions CD31. This is a surface antigen common to vascular endothelial cells, and is perhaps better known as PECAM-1 (platelet endothelial cell adhesion molecule - 1). This should only stain vascular cells.  Indeed, to date, nonvascular soft tissue tumors have been completely nonreactive to this antibody. This should help mitigate false positives.

You would also want to produce antibodies against a few other surface antigens common to the angiosarcoma (or any other unknown neoplasm for that matter). You would do this by introducing the neoplastic cells into a rabbit, for example. The rabbit mounts an immune response to the foreign cells in its circulatory system and produces antibodies specific to our unknown neoplasm.  

Using two or more types of mAb (Monoclonal antibody) to target the unknown tumor cells will increase the specificity of the staining/diagnosis process. It's important to note that key markers aren't always present on every cell of a neoplasm.

Here are some key markers for angiosarcomas that will help illustrate this point.

    * The ultrastructure of tumor cells includes intercellular and intracellular lumina with or without red cells.

    * In their cytoplasm, tumor cells contain intermediate filaments (vimentin, occasional tonofilaments [keratin]) and pinocytotic vesicles.

    * Weibel-Palade bodies, a marker of endothelial differentiation, may be seen in some cases.

    * The vast majority of lesions express vimentin and focally factor VIII–related antigen. Also expressed are CD34 (74%), BNH9 (an endothelial marker, 72%), and cytokeratins (35%).

    * Some of the tumors show actin expression, demonstrating a prominent pericytic component. Epithelial membrane antigen is not expressed, which helps to rule out a carcinoma.

    * S100 protein and gp100 (HMB-45 antigen, both melanocytic markers) also are not expressed; this helps to rule out melanoma.

    * Researchers have shown that anti-CD31 antibodies are one of the most specific endothelial cell markers. However, several other immunohistochemical markers (against factor VIII–associated antigen or the nonimmunologic binding to Ulex Europeans) should be used to avoid misdiagnosis.

So this explains a little about how you would differentiate an unknown neoplasm from related neoplastic pathologies.

Hope this helps get you started.  There's a few links below for some info on the topics I mentioned.

Best Wishes,

Jim

Answer 2

Wow. I'm barely going into my first year for a biological sciences major..... this question scares me.

Try calling some friends or a tutor for the answer.  Good luck!