Jun 25, 2012

My Old Love: Cytopathology

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!

Jun 16, 2012

Osteo YO!

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.

Jun 11, 2012

The Peculiar Field of Cardiology…

Cardiology is a field of medicine that is like no other. They are treating an organ that is essential for life, but they are rarely treating any tumors. Tumors are  so prevalent in any other organ system (GI, urinary, reproductive, respiratory, skin) so why are they not common in the heart? Well… It makes perfect sense. There are 3 groups of cells in the body based upon their proliferative capacity and relationship to the cell cycle.

The first group of cells are called labile cells. These are cells of the digestive tract, skin, respiratory tract, etc. and are dividing all the time. When cells are constantly dividing there can be room for error. These “errors” make the cells a little irregular. This is called dysplasia or pre-cancerous changes. If these irregular cells keep growing with errors these cells may become cancerous. Cells are at an increased risk to error due to irritation. For example skin that is constantly sunburned, or an esophagus that has reflux.

The second group of cells are called quiescent cells or stabile cells. These cells remain in Gap O of the cell cycle, but when needed the cell cycle can be stimulated for them to divide. Examples of stabile cells are liver cells, proximal tubules of the kidney and endocrine glands.

The third group of cells are non-dividing cells or permanent cells. These cells remain in Gap O of the cell cycle no matter what. Cells in this group include red blood cells, nerves, lens of the eyes and cardiac myocytes (heart cells). Makes sense now. This is why a person with a brain or spinal cord injury has permanent damage or why a person who loses their sight remains permanently blind. It also explains why patients can not survive massive heart attacks. The cells are not dividing to regenerate and repair the tissue . It also explains why tumors are not growing. The cells are not dividing to cause a neoplasia or cancer.

In the rare case of a tumor, the most common tumor of the heart is a metastasis. It is 30x more likely than a primary malignancy. Distant primaries are often melanoma, breast or lung. There can also be spread through the venous system (inferior vena cava) from the adrenal gland or the kidney. The tumor literally grows up the IVC into the right atrium of the heart.

The most common primary tumor of the heart is an atrial myxoma. 90% occur in the atrium and 80% of those are on the left side. These tumors are benign and occur in the 5th decade. Symptoms include breathing difficulty, shortness of breath, blueing of the fingers, dizziness, fainting, etc.

These tumors are semi-firm gelatinous nodules that are excised from the heart. They usually are brown-red and have the same external gross appearance.

The cut surfaces are brown-red and jelly-like.

The most common primary malignant tumor of the heart is a sarcoma. It is very important for the surgery, radiology and pathology team to determine if the lesion started in the heart or is a metastases from somewhere else. This will greatly effect the patients treatment. These patients have a poor prognosis overall, with survival of 12-24 months due to advanced stage at presentation.

This photo is of a rhabdomyosarcoma with cystic degenration.

Jun 11, 2012

Skin Condition: Vitiligo

A fellow employee has volunteered her hands for this post to demonstrate her skin condition, Vitiligo. Vitiligo is an autoimmune disease that attacks the melanocytes in the skin. Melanocytes are the cells in the skin  that are responsible for producing pigment. They determine what “color” your skin is. When these cells are destroyed there is no pigment being produced. These changes are more visible in people with darker skin colors. The effected skin feels normal but has no color and is more sensitive to sunburning. Vitiligo tends to occur on the face, the hands, body openings such as the mouth, belly button and genitalia and body folds such as the armpits.

Vitiligo affects between 0.5-1% of the population. About half of the people who develop this skin disorder experience some pigment loss before the age of 20, and about 1/3 of all vitiligo patients say that other family members also have this condition. Even though most people with Vitiligo are in good general health, they have a greater risk of having thyroid issues, pernicious anemia (vitamin B12 deficiency), Addison’s disease (decreased adrenal function), alopecia areata (round patches of hair loss), and uveitis (inflammation of the eyes).

Vitiligo frequently begins with a rapid loss of pigment, which may be followed by a lengthy period when the skin color does not change. Later, pigment loss may resume, perhaps after the individual has suffered physical trauma or stress. The loss of color may continue until, for unknown reasons, the process stops. Cycles of pigment loss followed by periods of stability may continue indefinitely. It is rare (but possible) for a patient with Vitiligo to repigment or regain skin color spontaneously. Most patients who say that they no longer have Vitiligo may actually have become depigmented and are no longer bothered by contrasting skin color. While such patients appear to be “cured”, they really are not. People who have Vitiligo all over their bodies do not look like albinos because the color of their hair and eyes may not change.

The above information fits for the most famous person that was said to have Vitiligo, Michael Jackson. Because he was visibly in the public eye as a dark skinned child, it was striking to see his skin color lighten so drastically over the years through his adulthood. Michael Jackson claimed he had the skin condition Vitiligo and still rumors were spread that he was “bleaching” his skin to have a lighter appearance. Even through his sex abuse trial, a victim claimed MJ had “spots” on his penis which fits with the diagnosis of Vitiligo.

If this photo is not altered, it can be indicative of a young MJ with the early stages of Vitiligo.

Now looking at skin color only (lol) , the difference in MJ’s skin is striking over the course of 20 years.

The only visible Vitiligo  involvement while wearing a long sleeve shirt and pants is on my coworkers hands. She told me while taking the photo that it used to be “worse” when she was younger. It fits with the disease.

Vitiligo is not curable at this time. If a small area (<50% of the body )is effected by Vitiligo, the patient is a candidate for repigmentation therapy. If the patient is not a candidate (<50%) they are a candidate for depigmentation (which most people aren’t a fan of). Those who go through with the depigmentation are usually satisfied with the results.

Disclaimer. All materials posted on my website are intended to showcase my love of pathology and art and the correlation between the two. In no way am I trying to exploit any patients or their specimens. All images and information should be used to educated people in the pathology field and enlighten others into my profession. Enjoy.