Chief Complaint: 48-year-old man with suspicious-looking mole on his back.
History: Max Burnell, a single, 48-year-old avid long-distance runner previously in good health,
presented to his primary physician for a yearly physical examination, during which a suspiciouslooking mole was noticed on the back of his left arm, just proximal to the elbow. He reported that he
has had that mole for several years, but thinks that it may have gotten larger over the past two years.
Max reported that he has noticed itchiness in the area of this mole over the past few weeks. He had
multiple other moles on his back, arms, and legs, none of which looked suspicious. Upon further
questioning, Max reported that his aunt died in her late forties of skin cancer, but he knew no other
details about her illness. Max is a computer programmer who spends most of the work week indoors.
On weekends, however, he typically goes for a 5-mile run and spends much of his afternoons
gardening. He has a light complexion, blonde hair, and reports that he sunburns easily but uses
protective sunscreen only sporadically.
Physical Examination: Head, neck, thorax, and abdominal exams were normal, with the exception of
a hard, enlarged, non-tender mass felt in the left axillary region. In addition, a 1.6 x 2.8 cm mole was
noted on the dorsal upper left arm. The lesion had an appearance suggestive of a melanoma. It was
surgically excised with 3 mm margins using a local anesthetic and sent to the pathology laboratory
for histologic analysis.
Questions:
1. How does the appearance of a malignant melanoma differ from that of a normal mole, or
nevis, on gross inspection (i.e. the macroscopic appearance)?
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melanomas are usually assymetrical (normal moles are usually symmetrical)
melanomas usually have an irregular border or outline (normal moles usually have a smooth
outline)
melanomas are usually not homogenous in color, often appearing to be several shades of brown
or blue in color (normal moles are typically one shade of brown)
if a mole is less than 6 mm in diameter (roughly the diameter of a pencil eraser), it is not likely to
be a melanoma
melanomas often have an uneven texture, with some areas raised above the skin and other areas
even with the surface of the skin (normal moles have a smooth texture and are either raised or
even with the surface of the skin)
melanomas are more likely to bleed or have a reddish halo around them (due to increased blood
flow)
2. Draw a normal mole and a malignant melanoma, as they might appear on the skin.
3. Why was it important to surgically excise and examine this mole?
The pathology report gave the followng description of the tissue sample: "Diagnosis:
Superficial spreading melanoma with vertical level V invasion. Coalescent nests of neoplastic
cells were noted in the papillary and reticular dermis and in the subcutaneous layer. In
addition, large pink-stained cells with pleomorphic nuclei were found spreading radially
through the epidermal layer. Proliferating lymphocytic cells are noted in the dermis
surrounding the malignant cells."
This mole looked like a melanoma, but the only way to diagnose a melanoma is to biopsy the lesion and
examine the cells under the microscope. Melanomas are particularly prone to metastasize to other parts of
the body, and once they have metastasized, they are very difficult to treat. In other words, there is a very
poor prognosis for the patient if the cancer has spread to other areas of the body.
4. What do levels I, II, III, IV, and V vertical invasion refer to when describing melanomas?
A. Level I - atypical melanocytic cells localized to the epidermis (i.e. they have not invaded through
the basement membrane)
B. Level II - melanoma tumor has just begun to invade the basement membrane and travel into the
papillary dermis
C. Level III - melanoma tumor is filling and expanding the papillary dermis, but has not yet invaded
the reticular dermis
D. Level IV - melanoma tumor has invaded the reticular dermis
E. Level V - melanoma tumor has invaded the subcutaneous fat layer
5. Why is it useful to determine the level of invasion of this lesion?
Determining the level of invasion of the melanoma is useful for two reasons: (1) It helps the physician
determine what type of post-surgical treatment, if any, to use, and (2) it helps establish a prognosis for the
patient.
If the melanoma has not metastasized yet, the 5-year patient survival rate for levels I through V are as
follows:
Level I - 99+%
Level II - 99%
Level III - 95%
Level IV - 75%
Level V - 39%
A. If the melanoma has already metastasized, the 5-year survival rates are as follows:
B. Metastasis to regional lymph nodes only (stage II melanoma) - 30% survival rate
C. Metastasis to more distant organs (stage III melanoma) - <10% survival rate
As is clear from the above statistics, the key to successful treatment of melanoma is to catch it early on in
its course, before it has invaded too deeply into the skin or metastasized. The treatments for metastatic
melanoma are unfortunately not very effective. Dimethyltriazenyl imidazolecarboxamide (DTIC) has been
used alone or in combination with other chemotherapeutic agents, but the response rate is only about 20 30%. Radiation treatment is used for palliative purposes only and usually only when the cancer has spread
to the bones or the brain. Other experimental treatments for melanoma include cytokines (interferons and
interleukins) and immunotherapy (monoclonal antibodies, autologous lymphocytes, and specific
immunization).
6. Propose an explanation for why proliferating lymphocytes were noted around the borders
of the lesion.
Our immune system not only helps protect us from infections, but also helps destroy cancer cells wherever
they form. Proliferating lymphocytes around the border of a melanoma most likely indicate that the
immune system is trying to develop a cell-mediated immune response against the cancerous cells. In fact,
the prognosis for a patient is better if such lymphocytic infiltration is noted. One possible reason why
cancers, in general, affect the elderly more commonly than they do younger individuals is that the elderly
immune system is not as effective in this cancer surveillance role as is the younger immune system.
Max is told that he has a malignant melanoma and that it may have already metastasized. He is
advised that he may need additional surgery to verify that his tumor has metastasized.
7. Why does Max's physician think that his cancer has already metastasized?
The suspicious-looking mole (later found to be a melanoma) was on the left arm. A hard, non-tender mass
was noted in Max's left axillary region (i.e. left armpit). This is where regional lymph nodes are located.
Thus, if Max's melanoma cells entered the lymphatic vessels under the skin, they would be carried to the
left axillary lymph nodes. The mass felt here is most likely an enlarged lymph node filled with proliferating
cancer cells.
8. What additonal surgical procedure might help Max's physician determine whether his
cancer has metastasized?
Surgical removal and histologic examination of the left axillary mass would ascertain whether or not Max's
melanoma has metastasized.
The surgical procedure alluded to in question #8 showed that Max's cancer had indeed spread
to another pary of his body.
9. How do malignant melanomas normally spread to other areas of the body?
Malignant melanomas spread first to regional lymph nodes via the lymphatic vessels, and then on to more
distant lymph nodes. They can also spread through blood vessels to virtually any organ of the body.
10. Describe some of the current theories of the etiology of malignant melanoma.
Sunlight (or other ultra-violet light exposure) and heredity have been implicated as risk factors for
melanoma. Those with fair-skin who sunburn easily are at greater risk than others. Multiple bouts of
intense sun exposure seem to predispose one to melanoma. Max is fair-skinned and has both a positive
family history of skin cancer (possibly melanoma) and a history of frequent sunburn and sunlight exposure.
He is therefore at increased risk for developing melanoma. The role of ultra-violet A and ultra-violet B
light is more well established in the etiology of other types of skin cancer (e.g. squamous cell carcinoma
and basal cell carcinoma) than it is in melanoma. Nonetheless, ultra-violet B light may directly alter the
structure of DNA in skin cells, and ultra-violet A light may inhibit the repair of that DNA damage. Thus,
skin cells exposed to ultra-violet light may undergo mutations which may play a role in their cancerous
transformation.
11. List two treatments available for Max's malignant melanoma, and comment briefly on
their effectiveness.
Determining the level of invasion of the melanoma is useful for two reasons: (1) It helps the physician
determine what type of post-surgical treatment, if any, to use, and (2) it helps establish a prognosis for the
patient. If the melanoma has not metastasized yet, the 5-year patient survival rate for levels I through V
are as follows:
Level I - 99+%
Level III - 95%
Level V - 39%
Level II - 99%
Level IV - 75%
If the melanoma has already metastasized, the 5-year survival rates are as follows:
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Metastasis to regional lymph nodes only (stage II melanoma) - 30% survival rate
Metastasis to more distant organs (stage III melanoma) - <10% survival rate
As is clear from the above statistics, the key to successful treatment of melanoma is to catch it early on in
its course, before it has invaded too deeply into the skin or metastasized. The treatments for metastatic
melanoma are unfortunately not very effective. Dimethyltriazenyl imidazolecarboxamide (DTIC) has been
used alone or in combination with other chemotherapeutic agents, but the response rate is only about 20 30%. Radiation treatment is used for palliative purposes only and usually only when the cancer has spread
to the bones or the brain. Other experimental treatments for melanoma include cytokines (interferons and
interleukins) and immunotherapy (monoclonal antibodies, autologous lymphocytes, and specific
immunization).
12. The incidence of malignant melanoma has increased over the past few decades. Propose
an explanation for this trend.
The incidence of melanoma has increased over the past few decades, with over 30,000 new cases reported
in the United States each year, mostly in the 15 to 50 year old age group. The most likely reason for this is
the increased exposure of the average citizen to sunlight, due to changing recreational habits, changing
clothing styles (with more skin now exposed to the sun), and a growing interest in looking tan.
Also, recent studies have correlated an increase in skin cancer to the gradual depletion of the ozone layer.
Studies in southern Australia, where clothing styles have not changed significantly, suggest this
relationship.