Melanoma is probably what most people think of when you think skin cancer. Melanoma is not the most common type of skin cancer though, but it is one the rise. It would probably be considered the nastiest skin cancer because of its ability to spread to other body sites and organs. We see anywhere from 2-5 specimens for melanoma a day from various parts of the body. There are multiple different variants of melanoma. Most commonly, melanoma arises from atypical changes that begin to develop in melanocytes. Melanocytes are the cells in the skin responsible for producing pigment or your skin color. These atypical changes usually occur in preexisting moles, or can form a new lesion, usually in Caucasian patients like the one seen below. Patients at the highest risk are usually light skinned individuals, who either live in sunny climates or spend lots of time in the sun, people who go tanning, people who burned or blistered as a child, relatives with a history of melanoma or certain individuals born with dysplastic nevi (atypical moles). Less commonly patients can form melanoma in areas of the body that are rarely or never exposed to the sun including the eye, the bottom of the foot, in between the toes, under fingernails and in the vagina.
This is a typical kind of specimen we would receive on a patient with melanoma called a LOCAL WIDE EXCISION. Basically the surgeon clearly cuts around the lesion, and we evaluate the surgical margins or the edge the surgeon cut, to determine if he removed all the cancer. The first thing I would do is measure this tumor and then measure how close it is to each edge. The most important margin in melanoma cases is not the sides actually its the bottom or deep margin. Melanoma tends to spread deep (vertical). This particular melanoma is about 2cm or almost 1″, pretty big for a mole…
This is a side view of the specimen. This shows how much subcutaneous fat tissue the surgeon cut out with the skin.
Next I will ink the subcutaneous fat tissue blue. This ink can be seen under the microscope and that is how the pathologist knows where the surgical margin is. Because melanoma produces pigment, microscopically these tumor cells can have a blackish color. Because of this, some pathologists prefer we do not use black ink to ink the surgical margin because it is too similar to the melanoma pigment, so I always encourage PA’s and residents to use another color with known melanoma cases.
This is a view of the inked deep margin, the most important margin in these cases.
Next I will serially section the specimen and lay out all my sections in a row. You can see that the lesion goes deeper into the subcutaneous fat tissue than it appeared before it was cut.
Next I will pick the section where I believe the tumor is coming closest to the deep margin. This will be the most important section for the pathologist to look at microscopically. In this slice I will first tell the pathologist that the tumor itself is 1.1cm in depth…
Then I will tell the pathologist that grossly the tumor comes to within 0.8cm of the closest approach to the inked deep margin. This section is what I tell PA’s and resident is the “money section”. This is the slide the pathologist needs to stage this patients tumor. Microscopically the pathologist will be able to see exactly how close the tumor cells are to the ink. The size of the tumor and depth of invasion all play a role in cancer staging.
The reason melanomas are such nasty tumors and spread easily can be easily appreciated now. The vertical growth of the tumor occurs when the melanoma invades deeper layers of skin. At this point the melanoma becomes dangerous as it now has the ability to enter either the blood stream or lymphatic system and spread to distant parts of the body.
The spread of melanoma through the blood stream is called hematogenous. For hematogenous spread to take place, melanoma cells must break away from the original tumor, find their way through a blood vessel wall and into the blood stream. When this happens melanoma can go to places such as the heart and brain.
Lymphogenous spread or the spread of melanoma by the lymphatic system occurs in much the same way as hematogenous. In the case of lymphogenous the melanoma cells travel through the lymphatic system and lodge in lymph nodes, which usually enlarge. Once the melanoma cells lodge in the lymph nodes they can spread to the vascular system.
When melanoma spreads from the original primary through the local lymphatic system and into the surrounding skin cells, they form what are known as satellite nodules. Satellite nodules are small deposits of melanoma cells spread around the original primary tumor. These present as palpable lumps usually in the vicinity of the original tumor.
The estimated 5 year survival rate of melanoma is as follows:
98% if cancer is found early before it has spread
62% if cancer has spread locally
15% if cancer has metastasized
Most people who really know me know that I am far more interested in gross pathology than microscopic pathology, despite my 2 recent posts. Microscopics definitely serve their purpose, but I am generally not interested unless it is something really cool. Like this…
Any pathologist or person with histology experience could easily tell you this is a benign lymph node microscopically with no patient history. What they could not tell you is what all this black pigment is…
This is actually what most of my lymph nodes look like microscopically, yes it’s tattoo pigment. This is what a lymph node looks like from a heavily tattooed person. Cool huh!?
When a person gets tattooed the tattoo ink is placed into the dermis of the skin, which is one of the deeper layers of the skin. The body senses the ink as foreign material and activates the immune response. The phagocytes of the immune system come in to “clean up” the pigment and they engulf the pigment particles. This is partially responsible for keeping the pigment in place. This is also why when a heavily tattooed person has an allergic reaction to anything all or some of their tattoos pop out or itch. As the tattoo heals granulation tissue (scar) forms. The pigment remains trapped within the cells of this scar. Its presence there is stable, but in the long term (decades) the pigment tends to migrate deeper into the dermis, accounting for the degraded detail of old tattoos.
Sometimes pigment migrates from a tattoo site to the lymph nodes, where large particles may accumulate, as seen in the photo above. When larger particles accumulate in the lymph nodes, inflammation may occur, which may enlarge the lymph node.
If an enlarged lymph node is palpated or seen on imaging, it can be recommended to the patient to get it biopsied or excised to rule out cancer.
Everyone is always asking me how I got into doing autopsies. I tell them my undergrad degree was in cytology and I was a cytotechnologist. Of course most people have no clue what that is…
Pathology is split into 2 divisions: Anatomical pathology and clinical pathology. Fields that fall under the division of clinical pathology include blood bank, chemistry, microbiology, virology, etc. Fields that fall under the division of anatomic pathology include surgical pathology, autopsy and cytology.
The word cytology in itself is the study of cells. Unlike surgical pathology and histology where we look at the entire architecture of the tissue under the microscope, in cytology we look at just the cells themselves individually. Because in cytology we are only looking at cellular changes, we can be very limited in what information we can give for diagnosis. Other times it is just enough information needed to make a diagnosis. It is definitely an essential part of the anatomic lab and is used in conjunction with surgical pathology often.
The most common cytologic examination people are familiar with is when woman go to the gynecologist and get a “Pap smear”. Those cells that are scraped from the cervix are placed in a vial and a microscope slide is made, or a microscope slide is made directly from the cervix. These slides are read by cytotechnologists to screen for precancerous cells. Since the implementation of the Pap smear by Dr. Papanicolaou the incidence of cervical cancer has dramatically decreased.
If a cytotechnologist detects precancerous cells on a Pap smear, they will send that slide to the pathologist for further review. If the pathologist agrees with the cytotechnologist, the pathologist will tell the gynecologist who will in turn will send the patient in for further treatment.
The treatment can be anything from surveillance to a small cervical biopsy, to a LEEP (loop electrosurgical excision procedure) or cone biopsy excision. This is where they try to remove all of the precancerous cells. These specimens would all be sent to my lab (which is surgical pathology) for us to examine the tissue architecture to give the patient a more firm diagnosis. If the cells remain precancerous the patient will be monitored. If the cells are cancerous the patient may require a hysterectomy. This is less common now because like I said earlier the risk of cervical cancer has dramatically decreased due Pap screening.
This is an example of what I used to look at as a cytotech. I would screen through hundreds of these slides a month. The big, flat, light blue cells that look like corn flakes are called epithelial cells. They are the normal cells that line the vagina and cervix. The little blue clustered cells throughout the photo are inflammatory cells called neutrophils or polys. This amount is pretty normal but can indicate that there is a recent infection. The 3 medium sized cells to the right of photo are abnormal. They are actually dysplastic or precancerous versions of the epithelial cells to the left. Having cells like this in a Pap indicates the patient was exposed to the HPV virus, probably type 16 or 18. These particular strains of HPV increase the patients risk of cancer . Viruses such as these are called oncoviruses. With recent inoculations of the HPV vaccine in young girls, the risk of cervical cancer is going to be even lower and less and less high grade lesions will be seen in Paps.
Below are histology photos of the cervix. In cytology school we did not just learn about cells, we also learned about the tissues the cells came from. This is called cytologic- histologic correlation. The photo to the left is the normal cervix. The photo to the right is the cervix with high grade dysplasia. Now you can understand cytology. When the gynecologist samples the cervix they are superficially scraping of the top layers of the epithelium to make a slide. In the slide you see normal cells and cells from the high grade (pre cancerous) lesion.
The cytology lab does not just receive Pap smears, they also receive specimens from any other organ system. Cerebrospinal fluid, peritoneal fluid, bronchial washings, bile duct brushings, urine, etc. Commonly, cytology is used because it is less invasive than surgical pathology. For example, if a patient has an enlarged thyroid gland, or and enlarged lymph node in their neck or armpit, their physician may first try to do an FNA on it or fine needle aspiration. They will make slides from the material taken from the needle. Sometimes this material is enough to say ” this is cancer” or “this is not cancer” or whatever the physician needs to know. Other times the FNA yields junk and an excisional biopsy is required.
Most people know I dropped out of HS early when I had my daughter and I missed lots of classes throughout school that other students took. My first science class in college was biology. I looked under the microscope on day one and fell in love. I asked my teacher if I could get a job looking under the microscope all day and she turned me on to the lab sciences. She was a medical microbiologist and told me all about careers in microbiology, hematology, cytology and histology.
I worked hard and in 4 years I graduated from Thomas Jefferson University with my degree in cytotechnology. I got hired right out of school and had a really cool job in a busy university hospital setting. Since cytology is a division of anatomic pathology, I was always curious about what was going on down the hall in surgical pathology and in the basement in the morgue with autopsy. So much so that when one of the surgical pathology technicians quit I was willing to give up my cytotech career to work in surgical pathology and go back to grad school to become a PA. The rest is kinda history!
Osteomyelitis by definition is infection of the bone. This infection can occur from direct extension or by hematogenous spread- meaning it can start from the skin or soft tissue and pretty much “eat” its way down to the bone (direct extension) or it can spread from another part of the body and spread via the blood (hematogenous). Osteomyelitis can lead to sepsis which is systemic infection of bacteria into the blood which can ultimately lead to death if left untreated.
A specimen with suspected osteo is considered a rapid because the medicine physicians are sometimes waiting to treat the patient depending what we see microscopically. Unfortunately bone tissue can not be processed as quickly as soft tissue because we can not cut it easily with a scalpel blade or the small delicate blade used to make the microscopic slides (microtome blade), which is similar to a very fine razor blade. So what most surgical pathology laboratories do is designate an area in the lab where all the bone tissues sit in this special solution called decal. Decal actually decalcifies the bone making it softer for us to cut with the bone saw, scalpel blades and the blades used to cut the microscopic slides. At my job I have been assigned to be the PA who tends to the “bone farm”. At any given time there is a rotation of any where from 5-15 bones that are being rotated from there fresh state, to the formaldehyde based fixative (formalin) to decal. This process can take anywhere from 2-5 days depending on what kind of bone it is, which is hardly “rapid” in some instances. Decal is not a miracle chemical. There are some risks involved with using it. It can effect histology (which is the appearance of the cells and tissues under the microscope) and if the bone is cancerous it can also effect how the tissue stains for certain tumor markers in the immunohistochemistry laboratory.
Here is an example of the typical type of specimen you would see for osteomyelitis…
This is a toe amputation that appears to have been surgically disarticulated at the metatarsal joint. Here you can see the toenail bed is present and the toenail is absent. A 1 x 1 cm gaping necrotic ulcer is identified on the dorsal surface of the toe in the subungual (under toenail) region. This ulcer has become infectious and its suspected to have eaten its way from the skin, through the subcutaneous tissue and into the underlying bone (direct extension). My job as a PA is to show the pathologist:
#1. Has the infection spread to the bone under the ulcer (osteomyelitis)?
#2 Is the infection approaching the margin (Where the surgeon cut it off)?
Well there are multiple ways to approach this specimen, but I want to do it the best way to give the pathologist the information he/she needs, yet not waste their time looking at unnecessary slides and wasting the lab money. So, with every specimen, we have to think about how we are going to section it. Often there are many ways.
In cases like this with a small toe, finger, or other organ/ tissue that can fit on one microscopic slide- I find it easier to show the pathologist the entire picture of what is going on. It will make sense below.
For example. Here if you cut the distal end of the toe off horizontally in the specimen above, you would only tell the pathologist what was going on in the bottom 0.2 centimeter of the toe. Then you would have to make another slide showing the ulcer with the underlying bone. That’s 2 slides and the pathologist can only say for certain that the infection is only 0.2cm away from the margin if he sees no signs of infection in that first slice. That is called an “en face” margin. This type of margin, in my opinion, is good only when the tumor or infection sight is grossly far, far away.
But… If you put colored ink on the resection margin and cut the toe in half along the long axis across the ulceration, you can show the pathologist what is going in the bone under the ulcer all the way up to the surgical margin. All on one slide!!!! This is called a perpendicular margin and is the best choice when the tumor or the site of infection is millimeters within each other.
Microscopically if osteomyelitis is present the pathologist will see many polys or neutrophils (which indicated a more acute infection) or lymphocytes (which indicates a more chronic process) under the microscope. These are all types of white bloods cells that indicate an infection. Sometimes even a portion of this tissue is sent to microbiology by the surgeon at the time of surgery to see what actual organism is growing.
After microscopic and microbial examination, the patient will or will not be given hard core IV antibiotics depending on results. If the infection persists and does not respond well to antibiotic therapy, further amputations may be required to save the patients life.
A current or past injury may make the affected bone more likely to develop the infection. A bone infection can also start after bone surgery, especially if the surgery is done after an injury or if metal rods or plates are placed in the bone. Other risk factors include diabetes, low blood flow and IV drug injection.
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