29 thoughts on “Questions and answers – Neoplasia

  1. I read that some cancers are more common in men than in women (e.g. lung, liver and bladder cancer) and vice versa (meningioma, thyroid cancer). Why is this? Could it be caused by hormones or some other factors or is it just a complete mystery?

  2. Most cancers show some differences in incidence between men and women. Despite or the obvious, where the organ of origin is only found in either men or women (!), including ovarian, uterine, prostate or penile cancer, both endogenous and exogenous factors may be involved. Hormones might influence the growth of individual cancer cells, for example in breast cancer, but hormones presumably is not the cause of the development of the cancer cells by themselves. The best known causes of gender differences are the exogenous, including smoking and alcohol comsumption. This explains why lung and bladder cancer is more prevalent in men than in women (smoking is still more common in men than in women) and why liver cell cancer (i.e. hepatocellular carcinoma) is more prevalent in males (more men drink excessively than women). In regions where viral hepatitis is endemic (e.g. South-East Asia; chronic viral hepatitis predisposes to development of liver neoplasia), this gender difference is not observed.

  3. Desmoplasia is one of the histological criteria for malignancy. However, loose, oedematous and newly formed connective tissue may be seen in a various of non-malignant (or non-neoplastic) conditions, so it cannot be used as the only criterion. However, when a desmoplastic stroma is found, one should try to rule out the presence of a malignant tumor.

  4. Excellent question.
    Answer: Both and neither. In most instances the tumor is named after the cells it resembles the most.For example hepatocellular carcinoma is composed of cells that resemble normal liver cells.But there are many exceptions and it is doubtful that some of these similarities are accurate.For example a low a well differentiated brain tumor composed of cells resembling astrocytes is called astrocytoma.High grade malignancy is called glioblastoma.What is a glioblast? OGK (only God knows). A tumor of the testis is called seminoma.Does that mean it resembles SEMEN? (I doubt it!!) Medullary carcinoma of the thyroid has a fancy name even though it is derived from C cells and there is no medulla in the thyroid.

    Synovial sarcoma does not originate from synovial cells and does not resemble normal cells lining the joint cavity.Uusually synovial sarcoma is not even related to the joint!!!
    Before I confuse you completely it i still safe to assume that the tumor’s name reflects the cell type the tumor cells resemble to the most.Fibroma is composed of fibroblastast, lipoma of lipocytes(fat cells). All these tumors most likley originate from some connective tissue stem cells that differentiate into tumor cells resembling the cells they are named after.

    Finally there are tumors that have eponymic names. These tumors are often of unknown origin. Ewing sarcoma does not originate from Ewing cell and does not resemble Ewing cell, since there is not such a cell!!

  5. 1) Do all malignant tumors metastasize?
    2) A teacher told me that brain tumors never metastasize outside the brain – why is this?

  6. In principle all malignant tumors can metastasize. However, local factors may influence the potency to invade the vessel walls in the organ of origin or the adhesion factors necessary for the intravasated tumor cells to adhere to foreign organ vessels. The first is probably the case for brain tumors, where the normal blood-brain-barrier might also be involved. However, the exact mechanisms are not known.

  7. Laura re #2:

    One of the possible explanations is that they kill the host before they have had the chance to invade and metastasize.I have seen brain tumors metastasize throught the surgical tubes that have been introduced to relieve the intracranial pressure.Throgh these tubes that are introduced into the cranium and implanted into the thoracic cavity the tumors may float and end up in the pleural cavity.
    Medulloblastoma of the cerebellum, a highly malignant tumor of childhood and young persons may give rise to “drop metastases”=cells are carried by the cerebrospinal fluid down to the terminal part of the spinal cord where they form secondary tumors .

  8. Laura #2:

    One of the explanations I have heard is that the brain tumors seldomly metastasize, because of the lack of lymph vessels in the brain. However, I do not have knowledge of any scientific support for this theory and it is probably only part of an explanation.

  9. Does anyone know of any relationship between the spread of tumors and lymph vessel representation in the given organ.

    There are always exceptions but usually carcinomas are lymphatic spread and sarcomas are hematogenous spread.

    Elspeth (Currently a second year med student at the University of Kansas, Ivan Damjanov is my mentor)

  10. Dear Elspeth,
    Very interesting question! There are probable several reasons for the differences in pattern of metastasizing you mention, including surface receptors, adhesion molecules and proteinases expressed by the tumor cells. However, several reports present data that the intratumoral formation of lymph vesssels (lymphangiogenesis) is different in different organs, see for example Anticancer Res 2009; 29: 1675 and Am J Pathol 2009; 175: 2235. Hence, it is not the density/number of lymph vessel in the original tissue. Whether this is also the reason why sarcomas almost never metastasize to lymph nodes I don’t know.

  11. Dysplasia denotes the morphological changes associated with pre-malignant and malignant mutations. I practice the term is used to describe pre-malignant changes in an epithelium, i.e. increased cellular proliferation and incomplete differentiation. Furthermore, dysplasias differ in severity.

    Anaplasia is an old term describing severe dysplasia, i.e. total lack of differentiation. The term has almost completely been replaced with the term ‘undifferentiated’.

  12. What is the difference between metaplasia, dysplasia and anaplasia?

    Is dysplasia a reversible process and as such a cellular adaptation?

    In the modern books on pathology, dysplasia is no longer mentioned in the chapters on adaptations but is instead mentioned in the chapters on neoplasia – is this an indication of dysplasia being a neoplastic condition? Anaplasia refers to completely undifferentiated cells and is somehow an outdated term or what?

  13. Dear Mette.

    You put several important questions on the disctinction between different cellular changes. Metaplasia is an adaptative and reversible process where one “well-differentiated” cell type is replaced by another “well-differentiated” cell type from the same germ layer. By “well-differentiated” I mean not permanently changed for example by genetic mutations.

    Dysplasia is not a reversible cellular change. Dysplasia occurs after genetic changes including formation and activation of oncogenes or disappearance or inactivation of tumor suppressor genes and is a precursor of malignancy. In practical pathology, it is often seen that early stage dysplasia can disappear and as such being reversible. However, it is rather a shedding of the diseased cells off the surface and not a molecular change.

    The last question is about anaplasi. Anaplasia is an anxient word meaning the total loss of differentiation. Although still used in some disease names, the word anaplasia has been replaced by “undifferentiated”. I find it most correct to use the grading high differentiated (=low grade dysplasia), low differentiated (high grade dysplasia) and undifferentiated.

  14. 1) Do all cancers stem from tissue which has undergone benign ‘transformation’ or may cancer evolve in completely normal tissue from ‘one day to another’?

    2) Which tumors most often progress from benignity to malignancy?

  15. Dear Anne,

    All human cancers have 5-10 rate limiting mutations which make them malignant. If the cells have less mutations than required to be a invasive cancer, they might look pretty normal, they might be hyperplastic, dysplastic, or they might form a benign tumor. Each of these stages might directly become a malignant cancer. So a benign tumor is not a mandatory stage preceding a malignant tumor. Often, however, benign tumor a quantitatively relevant precancerous lesions. This means that if you benign tumor, you have an increased risk for a malignant one. The relative risk for that is very much dependent on the tumor. For myeloma and lipoma it is very low, for polyps in the colon higher and for villous adenoma in the colon even higher.

  16. Hi Ehab,

    As far as I know:
    — Neoplasia ~ New growth (any kind of new growth, may be benign or malignant).
    — Dysplasia ~ Irreversible cellular change in which the cells in question change morphology to another cell type than their original. Prestage malignancy.
    — Anaplasia ~ Irreversible loss of cellular morphology. Malignancy.

    Try reading Ben Vainer’s description above (http://pathology.edublogs.org/2011/04/20/questions-and-answers-neoplasia/#comment-227).

    If I am not correct, could somebody please correct me?

  17. Dear Nikolaj,

    You are partly correct. Malignancy indicates invasion of a neoplasm, whereas the words dysplasia and anaplasia are linked to the morphological changes of the cells in the neoplasi. This means, that you can have an invasive tumor (i.e. cancer) with low-grade dysplasi or with high-grade dysplasi or an undifferentiated tumor. Anaplasia is another word for “undifferentiated” and means a neoplasm where the cells are almost not recognizable as to their cellular origin.
    Note, that you do have dysplasia in an invasive neoplasm (and the word therefore does not tell you whether the lesion is premalignant or malignant).

  18. well the discussion above regarding dysplasia and anaplasia is very interesting and useful but i would like to add few comments on it….
    we grade dysplasia into low, intermediate and high grade on basis of thickness of epithelium involved. if slightly less than entire epithelium is involved its categorized as severe dysplasia which in many books is also mentioned as anaplasia
    so anaplasia is simply severe dusplasia that is covering almost entire epithelium….but here its important to mention that full thickness epithelium involvement is carcinoma in situ , not dysplasia or anaplasia.

  19. We have discussed the transition between benign and malignant tumors in relation to mutations, and further mutations in relation to the various forms of adaptations described in pathology

    One teacher explains that all human cancers have 5-10 rate limiting mutations which make them malignant. If the cells have fewer mutations than required to be an invasive cancer, they might be hyperplasic, dysplastic, or form a benign tumor. Each of these stages may become malignant. For myeloma and lipoma transition is rare, for polyps in the colon more frequent and for villous adenoma in the colon even more frequent.

    Another teacher explains that metaplasia is an adaptative and reversible process where one “well-differentiated” cell type is replaced by another “well-differentiated” cell type from the same germ layer. By well-differentiated “I mean not permanently changed for example by genetic mutations”. Dysplasia occurs after genetic changes including formation and activation of oncogenes or disappearance or inactivation of tumor suppressor genes and is a precursor of malignancy.

    Questions:
    Do atrophy, hypertrophy, hyperplasia and metaplasia occur without mutations, whereas dysplasia occurs after mutations?

    Or may all forms include mutations, but some are arrested in benign reversible forms
    whereas others develop more mutations and become malignant:
    Mutations occur all the time but fortunately most of them are arrested and deleted – how does this fit with the terms benign and malignant as well as with the definition of reversible/irreversible adaptations?

  20. It is a question on how to define a mutation. A mutation is not a genetic alteration that is discovered and corrected by the cell – a mutation is a permanent alteration in the gene (i.e. not reversible). The adaptive changes, i.e. atrophy, hypertrophy, hyperplasia and metaplasia, are caused by changes in the external environment and does not need genetic changes in the cell type in question to occur.

    It is important to stress, that dysplasia is NOT an adaptive change, but occurs only after permanent genetic mutation in the genome. In some books dysplasia is mentioned as an adaptive change, but this is possibly because early dysplasia is “reversible”, that is the cells are shed off the surface and removed – the genetic change is still permanent.

    Is this answer enough? – otherwise, please feel free to write again.

  21. Additional note to Johannes’ Q:

    Malignancy is not defined by number of mutations, but is based on the degree and severity to which the histological and cytological criteria of malignancy are observed. Yet, malignancy is thought to arise as a result of accumulating mutations.

    • atrophy,hyprtrohpy,metaplasia and hyperplasia are cellular adaptive mechanism for external stimuli withou gene involvement. bty dyaplasia involve gene mutution

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