I felt maxed out in my previous position and was therefore looking for a position with more room for growth. The posting read as a Senior PA role specializing in neuropathology and hematopathology with skills in microscopic examination. I moved from Chicago to Boston’s Brigham and Women’s Hospital without hesitation, when I learned more about this pioneering position. The PA background is suited to this role, because we are trained to function at high-complexity levels. Although my knowledge in histology was rarely utilized in my prior PA work, this role gave me the opportunity to apply my histology skills, and to recognize patterns that are organ specific.
Now as a Pathologists’ Assistant, specializing in Neuropathology and Hematopathology, my current role is non-traditional. I am not in the gross room prosecting specimens. My function is to review cases in neuropathology and hematopathology, which includes ordering appropriate immunohistochemistry and molecular testing, interpreting results and preparing pathology reports for sign-out. At sign-out, I sit with the attending, and we go over my interpretations. The PA scope of practice dictates that we operate under the supervision of the pathologist, and it is the sole responsibility of the pathologist to render a diagnosis. The pathologist is still responsible for making a diagnosis; I help prepare all of the information and analysis in order for the pathologist to do so. The skill I use everyday were on-the-job trained through multiple modalities including reading the W.H.O. for my respective services. Furthermore, my training including sitting in on sign-out’s including molecular, brain cutting, tumor boards, and lectures as well as immersing myself in both fields. Following this training, I began working up my own cases and continued to learn through more hands-on training.
The following are two cases that begin to illustrate my workflow as the Senior Pathologists’ Assistant (PA) at Brigham & Women’s Hospital:
65 year old female with initial presentation of headaches for a 3-month period. Brain MRI shows a 3.0 x 2.6 x 1.0 cm T2 hyperintense lesion in the left temporal lobe with contrast enhancement. She underwent a craniotomy days later. The H&E slide shows dense cellularity, moderate to severe atypia, mitoses are present 5/10 hpf, vascular proliferation and necrosis are present. I order immunohistochemistry for IDH1 R132H and Ki-67 and molecular testing for MGMT promoter methylation, chromosomal microarray and oncopanel sequencing. The IHC results show: IDH1 R132H is negative, Ki-67 is at approximately 10% and MGMT promoter methylation is unmethylated. Diagnosis: GLIOBLASTOMA-IDH WILDTYPE, W.H.O Grade IV.
70 year old male with initial presentation of persistent low back pain and anemia. X-Ray identifies no lytic lesions. The bone marrow biopsy shows a hemorrhagic and apparently normocellular marrow (50% fat). Approximately 30% of the cellularity (20% of the intertrabecular space) is composed of a population of intermediate plasma cells occurring in small clusters as confirmed by immuno-peroxidase studies for CD138. Immunohistochemistry performed shows monotypic cytoplasmic kappa light chain restriction over lambda light chain. Of the remaining cellularity, the bone marrow biopsy shows the erythroid, myeloid, and megakaryocytes population are in normal proportion, exhibit maturation, and show no significant atypia. Bone trabeculae shows focal osteoblastic activity. Diagnosis: PLASMA CELL NEOPLASM.
I am passionate about our PA field and advocate for role expansion whenever possible. PA opportunities are the first step toward building momentum for profession-wide growth.
-Kristina C. Grieco, MS, PA(ASCP) is currently a Senior PA in Neuropathology/Hematopathology at Brigham and Women’s Hospital in Boston, MA. Her most recent project has been building the program Pathology Inspiration for Youth (PIY) to increase awareness of the pathology field among high school students and anyone exploring career opportunities in healthcare.
The patient is a 2.5 year old male who is being evaluated for
a liver transplant versus biliary diversion surgery. The patient was born at 2
kilograms and went home with mom one week after birth. The patient was
readmitted back to the hospital for evaluation of jaundice and since then the patient
has been intermittently hospitalized for episodes of worsening jaundice,
acholic stools, scleral icterus, and pruritus. At 5 months of age, the patient
was diagnosed with progressive familial intrahepatic cholestasis, type 2, and
was placed on the liver transplant list. As a result of the liver failure, the
patient has developed coagulopathy, hypocalcemia resulting in seizures, and
pruritus. The family history is significant for no known congenital
The father was worked up for living donation and was found
to be a suitable donor, and is donating the left lateral segment of his liver.
in the Surgical Pathology laboratory is a 700 gm, 23.5 x 14.5 x 3.5 cm
explanted liver with an attached 4.5 x 1.2 x 0.4 cm gallbladder. The liver
specimen has a smooth, green-red liver capsule without any grossly identifiable
nodules or lesions (Image 1). The gallbladder has a yellow-pink external
surface and is opened to reveal a 1.5 x 0.7 x 0.4 cm dark brown stone with a
small amount of brown-yellow bile fluid. The liver is sectioned to reveal a
smooth green-red cut surface (Image 2). No lesions are identified and minimal
hilar structures are included with the specimen. Portions of the specimen have
been taken for electron microscopy and frozen for future diagnostic purposes.
Submitted sections include:
1 and 2: Hilar structures
3-15: Representative sections of
16: representative section of
microscopy, the trichrome stain highlights the presence of portal and centrilobular
fibrosis, with focal bridging. However, regenerative nodule formation is not
evident. The portal tracts contain sparse mononuclear cell infiltrates. Significant
bile ductular proliferation is also evident, as confirmed by a CK7 immunostain.
However, the native bile ducts appear unremarkable. There is also considerable
hepatocellular and canalicular cholestasis in the centrilobular regions. Occasional
multinucleated hepatocytes are also seen within the centrolobular zones. No
steatosis is evident.
constellation of histologic features is consistent with the clinical history of
progressive familial intrahepatic cholestasis, type II.
Progressive familial intrahepatic cholestasis
(PFIC) is a group of autosomal recessive disorders that affects bile formation
and results in cholestasis of the liver, usually beginning in infancy and
childhood. There are three types of PFIC, each related to a mutation in the
liver transport system genes that are involved in bile formation. PFIC type 1
(PFIC1), which is also referred to as Byler disease, is due to impaired bile
salt secretion related to a ATP8B1 gene that encodes the FIC1 protein. PFIC
type 2 (PFIC2), which is referred to as Byler syndrome, is due to
impaired bile salt secretion (similar to type 1), but is related to the ABCB11
gene that encodes the bile salt export pump, or BSEP. PFIC type 3 (PFIC3) is
due to impaired biliary phospholipid secretion that is related to a defect in
the ABCB4 gene that encodes the multi-drug resistant 3 protein, or MDR3.
PFIC is suspected to be the cause of cholestasis
in 10-15% of children, and is also the underlying cause of liver transplants in
10-15% of children. The exact prevalence remains unknown, but is estimated to
be between 1 in every 50,000-100,000 births. PFIC1 and PFIC2 account for 2/3 of
all PFIC cases, with PFIC3 making up the other 1/3. PFIC is present worldwide,
and there does not appear to be a gender predilection.
The main clinical manifestation in all forms of PFIC, hence the
name, is cholestasis, and will usually appear in the first few months of life
with PFIC1 and PFIC2. Recurring episodes of jaundice are also present in PFIC1,
whereas permanent jaundice and a rapid evolution to liver failure are
characteristic of PFIC2. In PFIC3, cholestasis is noted within the first year
of life in 1/3 of all cases, but rarely will be present in the neonatal period.
PFIC3 can also present later in infancy, childhood or even early adulthood,
with gastrointestinal bleeding due to portal hypertension and cirrhosis being
the main symptoms that the patient would present with. Pruritus is severe in
PFIC 1 and 2, but has a more mild presentation in PFIC3. There have been multiple
cases reported of hepatocellular carcinoma that are associated with PFIC2, but
there so far have not been any cases of hepatocellular carcinoma reported that
are associated with PFIC3. Other signs and symptoms that may be present in
PFIC1 include short stature, deafness, diarrhea, pancreatitis and liver
steatosis. When examining clinical laboratory results, patients with PFIC1 and
PFIC 2 will have normal serum gamma-glutamyltransferase (GGT) levels, but
patients with PFIC3 will have elevated GGT levels. PFIC1 and PFIC2 can be
differentiated from each other by the higher transaminase and alpha-fetoprotein
levels that are found in PFIC2. When analyzing the biliary bile salt
concentrations, PFIC1 will have mildly decreased levels (3-8 mM), PFIC2 will
have drastically decreased levels (<1 mM), and PFIC3 will have normal
levels. In addition, the biliary bile salt:phospholipid ratio and the
cholesterol:phospholipid ratio will be approximately 5 times higher in PFIC3
than in normal bile, due to the biliary phospholipid levels being dramatically
decreased (normal phospholipid range = 19-24%, PFIC phospholipid range =
Histologically, PFIC1 and PFIC 2 will have canalicular
cholestasis, an absence of true ductular proliferation, and periportal biliary
metaplasia of the hepatocytes. In PFIC2, these manifestations are much more
worrisome with more marked lobular and portal fibrosis, and inflammation, as
well as having much more pronounced necrosis and giant cell transformation (Images
3 and 4). PFIC3 will show portal fibrosis and true ductal proliferation, with a
mixed inflammatory infiltrate. In addition, cholestasis can be present in the
lobule and in some of the ductules that contain bile plugs. Cytokeratin
staining can help confirm the ductular proliferation within the portal tract.
Mild or absent canalicular staining with BSEP and MDR3 antibodies will help to
diagnose PFIC2 and PFIC3, respectively.
A diagnosis of PFIC is based on the clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis (such as biliary atresia, Alagille syndrome, cystic fibrosis and alpha-1 antitrypsine deficiency). Ultrasonography of the liver will be normal with the exception of a possible dilated gallbladder. At the time of the liver biopsy, a portion of tissue can be submitted for electron microscopy, which in the case of PFIC, can show canalicular dilatation, microvilli loss, abnormal mitochondrial internal structures, and varying intra-canalicular accumulations of bile. PFIC1 will have coarsely, granular bile on electron microscopy, whereas PFIC2 will have a more amorphous appearance. If biliary obstruction is noted on the liver biopsy, a cholangiography will need to be performed to exclude sclerosing cholangitis. If a normal biliary tree is observed, as in PFIC, bile can be collected for biliary bile salt analysis (which was discussed earlier in the laboratory results section). Differentiating between PFIC1, PFIC2 and PFIC3 can be quite troublesome, but luckily Davit-Spraul, Gonzales, Baussan and Jacquemin proposed a fantastic schematic for the clinical diagnosis of PFIC, which is presented as Figure 1.
Ursodeoxycholic acid (UDCA) therapy should be considered in all patients with PFIC to prevent liver damage and provide relief from pruritus. Rifampicin and Cholestyramine can help in cases of PFIC3, but have been found to provide no improvement in PFIC1 or PFIC2. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. The total caloric intake should be around 125% of the recommended daily allowance. Dietary fats should come in the form of medium chain triglycerides, and care should be taken to check the patient’s vitamin levels to look for signs of vitamin deficiency. Patients with PFIC2 should be monitored for hepatocellular carcinoma, beginning from the first year of life. Ultimately, most PFIC patients develop fibrosis and end-stage liver disease before adulthood, and are candidates for liver transplantation. Diarrhea, steatosis and short stature may not improve after liver transplantation, and could become aggravated from the procedure. Hepatocyte transplantation, gene therapy or specific targeted pharmacotherapy are possible alternative therapies for PFIC, but will require more research and studies to determine whether they are viable options.
Davit-Spraul A, Gonzales E, Baussan
C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet
J Rare Dis. 2009;4(1). doi:10.1186/1750-1172-4-1
Evason K, Bove KE, Finegold MJ, et al. Morphologic findings
in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with
genetic and immunohistochemical studies. Am J Surg Pathol.
-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.
Jennison Hartong, MLS(ASCP)CM,
PA(ASCP)CM, is a Pathologists’ Assistant who recently went to
Ethiopia to teach grossing techniques. The editors of Lablogatory asked her a
few questions about her experiences.
Lablogatory: How’d you get involved with ASCP’s Center for Global Health?
Jennison: Dr. Milner, Chief Medical Officer of ASCP, initially reached out to one of the pathologists at M.D. Anderson to inquire if any Pathologists’ Assistants (PAs) would be interested in attending a workshop in Nigeria. I reached out and expressed my interest in teaching grossing techniques rather than public speaking (not one of my strengths). Dr. Milner then told me about this opportunity in Ethiopia where pathologists were requesting advanced, gross training in lymph node dissections on breast and colon specimens. I immediately jumped at the opportunity to help in this way.
L: What were your motivations for going?
J: Whether with basic health needs or more complex areas like cancer treatments, I’ve always wanted to use my education and experience to help others and impact lives in areas around the world where certain aspects of healthcare may not be accessible. Before becoming a PA, I was a medical technologist and was always interested in working with Doctors Without Borders, however, I did not have the years of experience to apply. I decided to go to PA school and was disappointed to learn that Doctors Without Borders does not utilize PAs. I figured that dream would have to be accomplished another way, which was why I was so eager to work with the ASCP and their global health initiatives.
Another motivation for going on this trip was
experiencing the work and organizational skills required for making a trip like
this successful. I am currently finishing my second master’s degree in public
health with a focus in health policy and management. I was very interested in
learning everything I could about planning programs to help developing
countries as well as being able to network with like-minded health
L: What did you hope to accomplish while you were there?
J: My main goal of this trip was to help advance Ethiopian residents and pathologists in certain grossing techniques. More specifically, I aimed to assist with lymph node dissections and, as it turned out, how to locate and sample the radial margin in colon cancer cases. I also wanted to experience a different culture than my own, step out of my comfort zone and challenge myself as a PA by teaching others. At the end of this experience, I can say that this trip was definitely a life changing experience and one I am extremely grateful for.
L: What did you learn about lab medicine in Ethiopia?
J: During my week in Addis Ababa, I quickly realized that it was up to me to make this trip as successful as possible. Never before in my professional career were all the decisions up to me, and at first, it was slightly uncomfortable. I was worried I would come across as too bossy or even condescending. However, after meeting Eshetu Lemma, the ASCP local representative, along with the other participants and experiencing their kindness and eagerness to learn, I was newly determined to make this trip an absolutely positive experience for everyone. I made some changes to the training sessions and after the first day, the rest of the week ran smoothly. I learned a lot about how lab medicine is practiced in Ethiopia. I learned that, in the case of a power outage, you carefully set your blade down and wait it out. I learned that resources like aprons and sleeves are not thrown away unless completely used up. I learned that due to cassette shortages, tissue submission is done quite thoughtfully- more so than in the United States. I learned that the overwhelming majority of cancer cases are presented at stage 4 due to issues surrounding resources, fear, myths, and lack of cancer education. But most importantly, I learned that the labs in Addis Ababa, Ethiopia, are doing an amazing job with the resources they are given and are eager for opportunities to positively impact patient care.
L: Is what you learned there applicable to your work in the States?
J: I’ll take what I learned there and incorporate it into my work here in the States. I’ve gained confidence in my ability as a health professional and reignited my passion to help others.
To put it simply, this trip has been life
changing. It has allowed me to experience and accomplish a lifelong dream for
which I am forever grateful. I’m hopeful that my future holds more
opportunities to serve other communities and help strengthen cancer programs in
-Jennison Hartong,MLS(ASCP)CM, PA(ASCP)CM is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology working mainly in oncology cases. Before attending graduate school, she worked as a Medical Laboratory Scientist (MLS) at Lurie Children’s Hospital of Chicago, Illinois. Upon graduating, Jennison started working at Memorial Sloan Kettering Cancer Center. In 2018, she relocated to Houston and currently works at M. D. Anderson Cancer Center in Houston, Texas. In May of 2019, Jennison will graduate with a second Master’s in public health with a focus in health policy and management from New York Medical College. She plans to use her extensive lab experience and newfound knowledge of public health to help bring basic healthcare to communities that would otherwise not have access to these necessities.