The patient is a 39 year old woman presenting with a
persistent cough. Upon work up, a pericardial effusion is noted. Pericardiocentesis
is performed and a smear made from the pericardial fluid reveals atypical lymphoid
Cytology of the
Additional imaging reveals an anterior mediastinal mass
measuring 12.6 cm. Excision of the mediastinal mass is performed.
Sections of mediastinal mass show a variable
population of lymphoid cells ranging from small to medium lymphocytes and some
atypical large lymphocytes. These atypical large lymphocytes have irregular
nuclear contours with abundant cytoplasm, vesicular chromatin and prominent
nucleoli. These atypical large lymphoid cells are consistent with Hodgkin
Reed-Sternberg cells. Abundant eosinophilic and scattered neutrophilic
infiltration are noted within the nodules. These nodules are surrounded by
dense collagen bands.
Immunohistochemistry studies are performed, atypical large
lymphoid cells are positive for CD30, Fascin and PAX5, while rare small to
medium sized lymphocytes are positive for CD20, however, large atypical
lymphoma cells are negative for CD20. Tumor cells are negative for CD3, CD5, CD15,
LCA, ALK and EBER ISH. CD3 and CD5 highlight the reactive T cells in the
Overall, the case is consistent with nodular sclerosis
classic Hodgkin lymphoma. The presence
of sheets of large lymphoma cells is suggestive of the syncytial variant.
Nodular sclerosis classic Hodgkin’s lymphoma (NSCHL) subtype
has a distinct epidemiology, clinical presentation and histology. NSCHL is more
common in females with peak aged between 15 and 34 years. The risk is higher in
high socioeconomic status. The patients are presenting with particularly mediastinal
mass and 40% B symptoms.
NSCHL can be distinguished from the other subtypes of
Hodgkin’s lymphoma (HL) with characteristic histologic features. There is a
nodular growth pattern and the nodules are surrounded by collagen bands
representing nodular sclerosis. The
lymphoma is composed of variable number of Hodgkin Reed-Sternberg (HRS) cells,
small to medium sized lymphoid cells and non-neoplastic inflammatory cells,
predominantly eosinophils, neutrophils and histiocytes. HRS cells have
multinucleated or binucleated with irregular nuclear contours and prominent
nucleoli. HRS cells induce fibroblastic activity by expressing IL-13 and the
fibrosis begins in the lymph node by invaginating into the lymph node along
Immunophenotypically, the lymphoma cells are mostly positive
for CD30 and 75-85% positive for CD15. Association with EBV can be demonstrated
with EBER in-situ hybridization. The
malignant lymphocytes in NSCHL are variably expressing CD20, PAX5 and CD79a,
however, T cell antigen markers, particularly CD4 and CD2 are aberrantly
expressed in NSCHL.
NSCHL is classified mostly as grade 2 and the prognosis is
better than the other subtypes of HL. Doxorubicin, bleomycin, vinblastine and
dacarbazine (ABVD) is the most frequent induction regimen for NSCHL patients
with over 70% response rate.
Patients with Syncytial Variant Nodular Sclerosis Classic
Hodgkin Lymphoma experience a lower than expected rate of complete therapeutic
response with shorter progression-free than non-SV NSCHL treated with standard
therapy. Syncytial Variant NSCHL should therefore be recognized as a high-risk
subgroup within the otherwise traditionally docile NSCHL classification. This
case fits the classic presentation for syncytial variant with presentation as
bulky (mediastinal) disease.
Eberle FC, Mani H, Jaffe ES. Histopathology of
Hodgkin’s Lymphoma. Cancer J. 2009 Mar-Apr;15(2):129-37.
Swerdlow SH, Campo E, Harris NL et al. WHO
Classification of Tumors of Haematopoietic and Lymphoid Tissues (Revised 4th
Edition). IARC: Lyon 2017.
Sethi T, Nguyen V, Li S, Morgan D, Greer J.
Differences in outcome of patients with syncytial variant Hodgkin Lymphoma
compared with typical nodular sclerosis Hodgkin Lymphoma. Ther Adv Hematol
2017, Vol. 8(1):13-20.
–Ayse Irem Kilic is a 2nd year AP/CP pathology resident at Loyola University Medical Center. Follow Dr. Kilic on twitter @iremessa.
–Kamran M. Mirza, MD, PhD, MLS(ASCP)CM is an Assistant Professor
of Pathology and Medical Education at Loyola University Health System. A
past top 5 honoree in ASCP’s Forty Under 40, Dr. Mirza was named to The
Pathologist’s Power List of 2018. Follow him on twitter @kmirza
When I was considering the Chief Medical
Officer role at ASCP, there was significant travel on the table. Prior to ASCP,
I was already a seasoned traveler, having been to every continent except
Antarctica. I had a few travel tricks up my sleeve. However, the nearly 2 weeks
per month that I find myself out of the ASCP offices have evolved my travel
skills from seasoned to ninja. For your enjoyment, here are some of my best
Join and explore a loyalty program. We all have frequent flyer miles with one or more airlines; however, consistent use of a single airline or group of airlines (Star Alliance, Sky Team, etc) will rapidly add up and provides perks and benefits you may have to research a bit. Most importantly, don’t get discouraged by one bad flight and switch! They are called loyalty programs for a reason. In addition to upgrades, lounge access, early boarding, and free premium snacks, perks like premium economy for the same price as economy make a huge difference as planes seats get tighter.
Book economy, fly business. Economy non-refundable tickets are the least expensive typically, especially when booked on a Tuesday. If you’re booking a common business commuter flight (Chicago to NYC, Boston to DC), make sure you’re staying over a Saturday and watch prices to book effectively over time. Typically, business customers book last minute (paying highest prices) so prices are lower when booked very early; however, commuter flights are often packed with business travelers so booking early may not always be cheapest. When you get to the airport, ask if upgrades to business are available when you check in but be patient! Booking the upgrade at the gate desk is often significantly cheaper. Set a limit for yourself. “I won’t upgrade unless the cost is less than $XXX.” This will keep your personal budgeting in check and not let your exhaustion or irritation with your last economy leg lead to something rash.
Plan ahead. If you’re planning a vacation, especially a long flight (not a typical business flight), research prices way ahead of time and watch them for some time. There are websites into which you can load your favorite flights and received pricing alerts. Even if you’re a business traveler (for example, attending conferences), you’ll likely know the dates early and be able to do the same. The earliest flights of the day are often the cheapest but remember the opportunity cost to you of having to get up extra early (especially if hauling little ones!).
Carry on. Don’t check a bag. There are exceptions but, for the most part, don’t check a bag. Consider the laundry services at your hotel or access to laundry machines. When you are packing, lay everything out and ask yourself, “Am I going to die if this is not with me?” If the answer is “no,” move to the “maybe” pile. If you’re bringing gifts, carry them in a reusable sack as your personal item. Speaking of reusable sacks, organizing your back pack with a few of these means you can pull out “computer” or “clothes” or “other” quickly and replace them easily (it’s like file folders). If you are going on a big trip and just can’t do without a checked bag, try to fly direct and/or make sure you have a full one hour (domestic) or two hour (international) layover between flights— both will increase the likelihood of your luggage arriving. If you are a business traveler, INVEST in a very good carryon bag. Because carryon luggage at the low end of the scale is assumed to never be checked, one bad flight can destroy it.
Toiletries. I know you have a strict beauty regiment with 12 products you can’t live without but consider lightening your load when possible. All hotels provide basic toiletries and there are stores everywhere (clearly, if you’re vacationing or working very remotely, there may be limitations, but remember context and consider the essentials). Most large format toiletries have to be checked and that’s adding challenges you don’t need. Some of my pro-travel colleagues who MUST have their complete hygiene system check bags but always use the suggestions I mention above about checked bag security. A clever, lovely friend of mine once said (when I asked why she was wearing only mascara in the middle of Africa), “If I just have this one thing I do every morning, I feel normal.” Sound advice.
Security. There is general anxiety about going through security but there doesn’t have to be. First, it’s for your safety and, unless you are a criminal or a terrorist, the security people are there for your protection and they are quite nice. Second, if you get TSA pre-check, know the drill. Nothing infuriates fellow travelers like a confused passenger in the TSA pre-check line disrobing and regurgitating the contents of their bag into a bin. If you’re not TSA pre-check, be ready to remove coats, shoes, laptop, belt, all pocket contents, and sunglasses. You can do all of that during your 10 + minute waiting in line. You should not do it when you get to the table—that’s why the line is so long. Third, when you travel internationally, the rules are always different but the security agents are still just human beings doing their job. Politeness and paying attention will make all the difference. Fourth, some of us are more likely to experience friction with security because of the way we look, our clothes, or even our perceived attitude. It’s not right, it’s not fair, and it’s annoying… but we know this and can prepare for it. Displaying courtesy and politeness at all points in the airport will get you through security quickly. If you happen to have a difficult experience, I encourage you to send a strongly worded, formal letter later (you can write it on your smartphone on the plane… just don’t send it until you are back home). There is no point in ruining your trip over someone else’s potential unfounded fear or ignorance. Lastly, I understand the world is liberated (being liberated) and we all think we have the freedom to do as we wish l; however, showing up to a security check point drunk or stoned or reeking of pot will get you heavily screened and searched. The rest of us enjoy the show but not the delays.
Boarding. The bin above your seat is not assigned to you. The space under the seat in front of you is. The bin above your seat is determined to be full by the crew, not by you. Other peoples’ bags are going to touch yours. The crew can and will place your bag correctly in the overhead bin. When you find your seat, quickly store your bags and sit quietly with your seatbelt unfastened and your hands in your lap. Don’t pull out your laptop. Don’t have 5 things in your hands and in the seat pocket. Your personal item under the seat in front of you should contain anything you’ll need during the flight. Organize yourself at home before you depart—not while the rest of the plane is trying to board. People will like you. The crew will like you.
Seat selection. If you know you get up frequently to use the restroom normally, book an aisle seat. If you pass out on airplanes at takeoff and wake up at landing, book a window seat. If you are in a middle seat (someone has to be), it’s frustrating but it does not entitle you to more space than the people on either side of you. Booking early and checking in early is the best way to score a window or an aisle. We are all trapped on the same plane and courtesy wins the day. If you are rude or discourteous, the crew will notice and you will have a miserable flight.
Jet lag. It happens. It’s terrible. It can take you out for a day or more of your trip. There are apps and websites that explain how to avoid, reduce, or beat jet lag. But each person’s physiology is different and these remedies may fail. Common chemicals used include melatonin and caffeine. You’ll have to find your own way of coping but, for fun, here is mine. First, sleep when it’s dark and stay awake when it’s light. Avoid napping during the day. Second, if you are on an overnight flight to an earlier time zone (US to Europe), do your best to sleep on the plane. I don’t recommend drugging yourself but earplugs and an eye mask can do the trick. Lastly, the first night you are in your final destination and about 1.5 hours before bed, run a hot bath and drink a very cold beverage (beer is my preferred coolant but anything cold, with calories, and no caffeine will work). Turn the AC down to a low setting so the room is chilly (even if it’s winter).The hot bath relaxes your muscles, shifts your blood flow, and tells your brain to cool down your body. The cold liquid helps do this. Why? We are naturally diurnal and our bodies are warmer when we are awake than when we are asleep (and the switch is related to light cycles and perceived time of day). After the bath, don bathrobe or towel and sit in the cool room for 15 to 30 minutes so your body dries with water on it (more cooling effect!). Now that you are chilled, crawl in bed and sleep. As I said, this works for me and it may not work for you. And, of course, it requires a bathtub.
Consumption. Drink plenty of water. Deep vein thromboses are no laughing matter. Being well hydrated and getting up to use the restroom a few times is actually good for you. Don’t drink tea or coffee on an airplane (google it to see why). If you’re on an international flight and the alcohol is free, pretend you’re at your grandmother’s house. A glass of wine or a cocktail are fine but becoming inebriated will do you no favors. It can also cause you to sleep when you shouldn’t and it dehydrates you. Make your own choices about eating food on the airplane. It’s often hit or miss so my decisions are made in real-time.
self-explanatory one-liners to wrap up:
Wear comfortable, slip on shoes
Loose fitting pants (with belt)
Leave you giant pillow at home
Headphones! No exceptions
Ziplock bags to organize electronics
Always have a pen
Seats are for people, not bags
Understand time zones in advance
Learn “Hello” and “Thank you” in the local language
Carry at least two universal travel adapters
-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.
A 58 year old female presented to the emergency department with a chief complaint of shortness of breath, fevers and chills since the previous day. Her past medical history is significant for chronic obstructive pulmonary disease, hypertension, and borderline personality disorder. Vitals signs were significant for an oxygen saturation of 88%. Physical examination of the patient was difficult as the patient became increasingly agitated, however, the patient appeared in no acute distress with moist mucous membranes, anterior lung fields were clear to auscultation, there were no cardiac murmurs, and examination of their skin revealed no rashes or lesions.
Laboratory tests were significant for a lactate level of 2.5 with a white blood cell count and complete metabolic panel within normal limits. Chest x-ray did not show evidence of consolidation or interstitial infiltrates. Urinalysis was within normal limits. One set of blood cultures was also drawn during this initial encounter. The patient became increasingly agitated after initial examination and was discharged with some laboratory tests pending. After incubating for 20 hours, the aerobic blood culture bottle flagged positive for bacterial growth, with gram stain demonstrating a gram negative coccobacillus and a rapid Verigene identification of Acinetobacter. The patient came back to the emergency department the next day with stable vital signs and unremarkable complete blood count and chest x-ray. The patient was started on meropenem which was switched to ciprofloxacin two days later, after bacterial antibiotic susceptibility results showed susceptibility to carbapenems, amikacin, amp/sulbactam, ceftazidime, ciprofloxacin, gentamin and tobramycin.
Acinetobacter is a
genus of gram negative bacteria, with some genospecies identified as human
pathogens including species in the A.
calcoaceticus-A. baumannii complex (ACB) which are difficult to
differentiate by phenotypic characteristics. Species in the ACB include genospecies
1 (A. calcoaceticus), genospecies 2 (A. baumannii), genospecies 3, and
In the laboratory, Acinetobacter
appear as non-pigmented mucoid, domed colonies with a smooth surface on growth
media. Acinetobacter are non-motile,
aerobic, catalase positive, oxidase negative, indole negative bacteria. Acinetobacter are also non-glucose
fermenters and do not utilize lactose.
Out of the ACB genospecies, A. baumannii is considered the most significant pathogen, causing
80% of nosocomial infection. A. baumannii
is an environmental bacteria which inhabits soil and water. In hospital
settings, A. baumannii can survive on
environmental surfaces for extended periods of time and is resistant to
desiccation and cleaning solutions. The most common settings in which A. baumannii infections occur are within
intensive care units where there are immunocompromised patients utilizing
medical devices such as ventilators or catheters which are surfaces A. baumannii frequently colonizes. Not
surprisingly, sites where these medical devices preside are the most common
sites of infection for A. baumannii
including the respiratory tract (hospital acquired pneumonia), bloodstream
infections, and wound infections. Interestingly, A. baumannii wound infection have also been seen at a high prevalence
in wartime and disaster victims. A.
baumannii has been recovered in 63% of wounds from soldiers in Iraq and Afghanistan
and 20% of wounds from victims after a tsunami in 2004.
Importantly, A. baumannii can be resistant to several classes of antibiotics including fluroquinolones (DNA topoisomerase mutations), aminoglycosides (transposons), beta lactams (AMP C beta lactamase), and carbapenems (OXA carbapenemase), making infections with multidrug resistant organisms challenging to treat. In this case, the microbe had an OXA carbapenemase but was susceptible to carbapenems. In addition, this patient’s relatively benign presentation and normal laboratory results raise the question of whether this bacteria was causing a bloodstream infection or was simply a skin colonizer which grew after being inoculated into the blood culture media. Acinetobacter, in addition to colonizing hospital equipment and surfaces is a common colonizer of the skin as well as respiratory tract of patients on respiratory ventilators. Thus, Acinetobacter can be inadvertently cultured in blood and sputum samples, making correlation of the patient’s clinical symptoms and signs with culture results very important.
-Liam Donnelly, MD is a 1st year anatomic and clinical pathology resident at the University of Vermont Medical Center.
-Christi Wojewoda, MD, is the Director of Clinical Microbiology
at the University of Vermont Medical Center and an Associate Professor
at the University of Vermont.
Generation X is sandwiched between the two largest generations alive today: Baby Boomers and Generation Y/Millennials. This means that Generation X will never be the largest generation at the workplace, but even so, their impact is significant. Gen Xers are in a unique position as they started their careers relatively recently and can understand the challenges Millennials face, while also starting to enter leadership positions and can therefore relate to Baby Boomers.
One of the things that make Generation X stand out from
other generations is that many of them have young children and aging parents.
This means that having a work-life balance is important to them as they often
have responsibilities to take care of their family members. They typically also
prefer a divide between their personal and work lives. This is not to say that
they do not make friends at work or not hang out with colleagues after work,
but they tend to have a “business first” approach to their work relations.
When working with Generation X, note that they appreciate it
if you use their time efficiently. When presenting an idea of have a meeting
with them, make it as productive as possible and focus on what is in it for
them. Gen Xers value brevity, fast turnarounds, and efficiency. This is a stark
contrast with Baby Boomers, who focus on interpersonal relationships before
getting a task done. Making your communication, whether it is in-person, over
the phone, or via Gen X’s preferred mode of communication (email), as concise
and to the point as possible will increase your effective collaboration with
As leaders, Gen Xers dislike micromanagement, both as a leader and as a follower. Their leadership style revolves around trusting others to get the job done and they expect the same courtesy in return. They value people doing what they say they are going to do, so do not promise Gen Xers that you will do something if you know you cannot. Their leadership style is therefore quite informal as they expect people to follow deadlines and get the job done, while giving their workers a high degree of freedom.
Generation X is an efficient generation who hate wasting time with empty words, promises, and incompetence. They appreciate immediate actions, a focus and straightforward approach to work without long social interactions. They respect child-friendly environments, such as being able to have a flexible schedule that allows them to accomplish their professional tasks while also taking care of their family members. They can brief and blunt, but they have an authentic and results-orientated approach to work. If you work with a Gen Xers, give them freedom to do their work and explore and only make promises you can keep. Keep your emails and interactions to the point and follow up quickly after a meeting. Having an efficient but friendly approach will take you far with this generation.
-Lotte Mulder earned her Master’s of Education from the Harvard Graduate School of Education in 2013, where she focused on Leadership and Group Development. She’s currently working toward a PhD in Organizational Leadership. At ASCP, Lotte designs and facilitates the ASCP Leadership Institute, an online leadership certificate program. She has also built ASCP’s first patient ambassador program, called Patient Champions, which leverages patient stories as they relate to the value of the lab.
So what does working with a Gen Xer really mean? Does it
only apply to the laboratory, or do we work with people outside of the
laboratory? Hmmm. How about our family, friends, social and community
relationships? That said, I took this question to the streets as well as the
laboratory and asked these questions.
Boomers, what’s it like working with a Gen
Gen Xers have a good work ethic; however, their family often
ranks higher than their job. Boomers pride themselves in their work ethic. The
Gen Xers are still so busy taking care of their aging parents, as well as,
their kids, even when they’re off at college. They are the “Sandwich
Millennials, what’s it like working with a
I took this question to the classroom where I teach. My
students are all working on their Masters Degree, and by the way, I have three
Gen Z students in my class. Both the Millennials and Gen Z students found that
the communication with a Gen Xer is different. The stated that the Gen Xers use
email, messaging and Slack. As a Boomer, I didn’t know what Slack was! The
Generation Y and Z students felt that the Gen Xers were resistant to change and
to some technology.
One Millennial by the name of Erika shared that she found
Gen Xers relatable and at ease. I found her most profound statement to be that
she said the Gen Xers seemed like they were in-between and strike a balance
between the Boomers and the Millennials. Hmmm…. They are known as the “Sandwich
Generation” because they are often taking care of their parents and their
children, but it’s interesting Erika saw them “sandwiched” in a different way.
Time to hear from
our Gen Xers and how they feel about working with the Boomers and Millennials.
Gen Xers, what’s it like working with the
Boomers and Millennials?
My first Gen
X interview came from a regional director of a Beverage Company. As a Gen Xer,
he felt that he was more effective working with the Boomers when the
communication was face to face, or on the telephone. Emails worked, but he
definitely noticed the Boomer preference. On the other side of the coin, this
Gen Xer found that the Millennials who worked for him or with him preferred the
The Gen X laboratory
professional I interviewed found the Boomers resistant to change. This was
interesting because this is how the Millennials felt about the Gen Xers! Again,
is this the “Sandwich Effect!” Overall, this Gen Xer appreciated the depth and
vast knowledge of the Boomer and how they wore that hard work as a badge of
Lastly, on a
high note, the Gen X laboratory professional really appreciated the Millennial’s
enthusiasm. The grass doesn’t grow under their feet in the work place. If they
perceive there’s no place to climb the ladder, they’re off and running. The Gen
Xers let go of the “Boomer Job Loyalty Program,” however, they are more stable
than the Millennials in the work place. Again, they possess the gifts from the Boomers
and Millennials. They are “The In-betweeners!”
-Catherine Stakenas, MA, is the Senior Director of Organizational
Leadership and Development and Performance Management at ASCP. She is
certified in the use and interpretation of 28 self-assessment
instruments and has designed and taught masters and doctoral level
As pathologists, we are
responsible for increasingly intricate anatomic pathology and clinical
laboratory services in a continually changing healthcare landscape that requires
us to integrate emerging technologies for improved quality of medical care
while also being hypervigilant to cost control and efficiency. Hospital systems
working under managed care business models seek to expand their coverage
networks and boost the number of patients served, and as such, it is going to
be very critical for the next generation of pathologists to develop and
implement the management skills and techniques necessary to effectively advocate
for investment in their departments and meet such goals.
The problem, however, is
that we are largely shielded from these issues during our undergraduate and even
graduate medical education experiences. We focus, of course, on the basic
sciences and clinical skills, which are undeniably important; however, we get significantly
less instruction or discussion on functioning within our health care system,
addressing quality issues, or general leadership training that is indispensable
and highly valuable for practicing physicians.
Earlier in the summer, I
saw a number of pathology folks on Twitter promoting and strongly encouraging
residents to apply for the two-day “Just Say Know! From Mentoring to High
Performance” program, formed through collaboration between ASCP and USCAP, on
an approach to leadership, management, and business for pathology. I was highly
intrigued and had a feeling this program was the sort of experience for which I
had been looking. Traveling to Palm Springs in the middle of the Chicago winter
was not a bad deal either!
Drs. Blair Holladay and David
Kaminsky assembled an impressive collection of speakers for the weekend, which
was divided into four focus areas: leadership, management, business and policy,
and change. After an engaging introduction by Drs. Holladay and Kaminsky,
current trainees Drs. Kabeer Shah and Melissa Hogan set the stage by
highlighting the increasing importance of “management” and “leadership” as
reflected in the ACGME milestones as well as recent literature suggesting
expectations for newly-trained pathologists include these very skills (Post et
al. Arch Pathol Lab Med 2017;141:
193-202).Above all, they encouraged
all of the thirty residents and fellows in attendance to “be honest, be open,
and be vulnerable,” and ask the tough questions of themselves to gain the most
from the weekend.
Lotte Mulder from ASCP led
an enlightening discussion on the differences between emotional intelligence
(EI) and conventional IQ, as well as the critical need to be self-aware of how
our emotions can affect our performance and to understand the extent of our own
abilities, strengths, and weaknesses. Dr. Karen Kaul followed with a very
timely overview of strategies for identifying mentors. She discussed how our
mentorship needs will evolve over the course of our careers and that fulfilling
the mentor role for another junior individual while having your own mentors is
key to the professional development necessary in leadership positions.
After lunch, Dr. Dan Milner from ASCP took us
through some very interesting global health case studies that forced our group
to think critically about the role of pathology and the clinical laboratory in
underserved settings as well as the major obstacles and economic disparities
that must be considered. There were a number of important teaching points from
Dr. Milner’s international cases that will be equally helpful for understanding
the disparities we encounter right here in our backyard.
Dr .Yael Heher led off
the afternoon management focus series with a really comprehensive look into how
she has championed quality improvement and patient safety reviews at her
institution to address root causes for laboratory errors, followed by a
well-timed interactive session in which we divided into groups to use the six
sigma methodology to work in concrete steps through a real-life laboratory
error. It was a great opportunity to see people from different institutions and
backgrounds bring unique perspectives to a common problem. The first day of the
program concluded with a very unique session on art and leadership in which Dr.
Kaminsky led us into Downtown Palm Springs to view the Palm Springs Babies art
installation set up by David Cerny. Our powers of observation as pathologists
were put to the test as we were asked to describe and interpret the meanings
behind the exhibit in the same way that we often use visual evidence in our
The second day of the
program focused on business and policy with talks by Dr. Gary Procop on how
pathologists can help integrate interventions into the laboratory to improve
system-level metrics and by Khosrow Shotorbani on how laboratory data can be
used to optimize laboratory services in the model of the rideshare service,
Uber. The morning also included an interactive session on negotiation skills,
in which each of us assumed the roles of departmental chair and owner of a
private practice group negotiating with newly-hired pathologists. The weekend
concluded with Dr. Nathan Johnson’s 18 steps to make change a part of an
organizational culture, which was based on his experiences in academic
research, military operational theory, and real-life lab experiences.
The weekend provided an incredibly impactful and high-yield array of discussions, so much so that I am already finding myself applying many of the strategies and techniques described over the weekend in my role as chief resident as well as to some of the changes and initiatives that I am hoping to bring to our department. Most important, though, were the opportunities to interact with my peers from around the country. We all face similar challenges as residents, and the opportunity to learn each other’s perspectives and approaches to similar issues was just as illuminating as the structured portions of the program. I hope that the ASCP and USCAP continue to offer the Just Say Know! Program and enthusiastically join all those pathology folks on social media promoting the program last summer with my own strong recommendation to challenge yourself and be open to new ways of learning by considering participating in this event!
-Imran Uraizee, MD, is currently chief resident and a third-year anatomic and clinical pathology resident at the University of Chicago. He also manages the Department of Pathology Twitter account, @UChicagoPath. He majored in Biology at Duke University before earning his MD at the University of Rochester School of Medicine and Dentistry. Dr. Uraizee can be followed on Twitter at @IUraizee3MD.
43 year old man presented with symptoms of superior vena
cava syndrome including swelling of the head and neck and difficulty breathing.
He was found to have a 9 cm anterior mediastinal mass on imaging.
Sections show fragments of fibrotic tissue with crush
artifact. Two distinct morphologies are seen in different tissue fragments.
Some tissue fragments show infiltration by cords and aggregates of abnormal
large lymphoid cells with irregular nuclear contours, somewhat vesicular
chromatin, small nucleoli and small to medium amounts of cytoplasm. Frequent
apoptotic cells and mitotic figures are seen. In other tissue fragments, the
large cell component is absent and there are focally vague nodules. The nodules
are composed of small mature appearing lymphocytes, rare eosinophils and
scattered medium and large mononuclear and multinucleated cells with prominent
nucleoli consistent with Hodgkin cells and Reed-Sternberg cells, respectively.
Admixed histiocytes are also seen.
By immunohistochemistry, the areas with different
morphologies also show different staining patterns. The areas with the large
cell infiltrate are immunoreactive for CD20, BCL6, and MUM1, dimly positive or
negative for CD45 and negative for CD10. CD30 is variably positive in the large
cell population and CD23 is largely negative. CD15 shows a golgi staining
pattern. The Hodgkin and Reed-Sternberg (HRS) cells present in the areas
without the large cell infiltrate are brightly immunoreactive for CD30 and CD15
(membranous and golgi pattern), dim positive for PAX5 and are negative for
CD20. CD20 and PAX5 highlight small B-cells present in aggregates surrounding
the HRS cells. By Ki-67 staining, the proliferation index is high (90%) within
the diffuse large cell component and also highlights the HRS component.
Overall, the findings are of a composite lymphoma composed
of both a diffuse large B-cell lymphoma (DLBCL) and a classic Hodgkin lymphoma
Composite lymphomas occur when two morphologically and
immunophenotypically distinct lymphomas occur at the same anatomical site. They
are most commonly composed of two Non-Hodgkin B-cell lymphomas (NHL), however
rare cases of composite CHL with NHL have been reported. In a review of the
literature, Goyal et. al. documented 20 previously reported cases of composite
lymphoma with CHL and DLBCL components. The median age at presentation was 51
years with 12 men and 9 women. Fifteen of the cases presented with nodal
involvement and of those, three had mediastinal disease. The most common
subtype of CHL was nodular sclerosis. Evaluation for IGH gene rearrangements
was performed on both components of 6 cases, with either a complete or partial
clonal relationship between the components seen in all of the cases tested. This
suggests a shared origin from a common B-cell precursor.1
A review of literature by Wang et. al. documented 10
previously described composite lymphomas consisting of DLBCL and CHL. The most
common site of occurrence was in lymph nodes, followed by three cases seen in
the stomach, one case in the small intestine and one case in the anterior
mediastinum. CHL is more commonly associated with EBV infection than NHL In the
reviewed cases, 6 showed positivity for EBV infection in both the DLBCL and CHL
components. This suggests that the lymphomas shared a common EBV-infected
progenitor cell, and are also clonally related as seen in the Goyal review. 2
Composite lymphomas must be distinguished from another WHO
defined entity called B-cell lymphoma, unclassifiable, with features
intermediate between diffuse large B-cell lymphoma and classic Hodgkin
lymphoma. This entity has previously been referred to as “grey-zone lymphoma.”
These lymphomas tend to present as mediastinal masses and can cause superior
vena cava syndrome. They show a wide spectrum of histologic appearances within
a single tumor and often show sheet-like growth of pleomorphic cells. Some
areas may resemble CHL while others resemble DLBCL. The neoplastic cells
typically do not show the characteristic immunophenotype of either CHL or DLBCL.
Areas that may resemble CHL will show preservation of B-cell markers, while
areas more characteristic of DLBCL might lose B-cell markers and express CD30
and CD15. These tumors will show clonal rearrangement of the immunoglobulin
genes. They tend to have a more aggressive clinical course and worse outcome
than either CHL or DLBCL. 3
This case was ultimately diagnosed as a composite lymphoma
(CL) because it consisted of separate areas with the morphologic and immunophenotypic
features of both classic Hodgkin lymphoma and diffuse large B-cell lymphoma. Patients
tend to have a poor prognosis with short survival. There is no standardized
treatment for composite lymphomas due to their rare occurrence; however cases
with a component of DLBCL are generally treated with aggressive chemotherapy
such as R-CHOP.
Goyal, G. et al. “Composite Lymphoma with
Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma Components: A Case
Report and Review of the Literature.” Pathology – Research and Practice vol.
Wang, Hong-Wei et al. “Composite diffuse large
B-cell lymphoma and classical Hodgkin’s lymphoma of the stomach: case report
and literature review” World journal of gastroenterology vol.
Swerdlow SH, Campo E, Harris NL, et al. WHO
Classification of Tumours of Haematopoetic and Lymphoid Tissues (Revised 4th
edition). IARC: Lyon 2017.
–Chelsea Marcus, MD is a Hematopathology Fellow at Beth Israel
Deaconess Medical Center in Boston, MA. She has a particular interest in
High-grade B-Cell lymphomas and the genetic alterations of these
Okay-okay, I couldn’t resist that. How many times have you
just wanted a CSI-style joke on here?
No? Just me? That’s fine…
Hello again everybody! Welcome back! Last month I talked a
bit about “Just
Culture,” a sort of bridge between the values we tout as clinical leaders
in our laboratories and the medical culture’s evolving and value-informed
paradigm shift. There was a little in there about the lessons paralleled in LMU
and the benefits of interdisciplinary teamwork. This month, on the subject of
interdisciplinary collaboration, I’d like to talk about our colleagues who often
are secluded or in more remote areas in our hospitals, offices, and academic
centers. Not here to stereotype; I’m talking about our friends in forensic
Before I get there, let me go back a bit. I’ve already written several times about the stereotypes that surround our field of lab medicine and there are two times when that is glaringly present: when you’re a medical student or when you’re in forensics. I got the chance to meet someone who falls into both categories.
I’ve just finished up my OB/GYN rotation. But before my last
day, I went to the lab at our hospital and followed up on some pending biopsy
results. Okay, I can’t lie to you guys: they wanted me to see if I could rush
“my lab friends” to expedite the process of fixing, setting, cutting, staining,
and reading/reporting—because that’s
possible. So, I went to the lab and had a pleasant chat with the staff
explaining the situation and they were happy to help. While I was there,
however, I happened to see another short white coat (ironically from my same
school) who was helping some lab personnel with some grossing. Turns out she
wants to match into a pathology residency—just like me—and specifically was
interested in forensic path, a field which I don’t know much about. After talking
more, I asked if she’d like to share some information. Here’s my conversation
with Kyla Jorgenson, a 3rd year medical student at AUC-SOM from
I get lots of hassle
when I say I want to become a pathologist. People often ask me, “what’s your
back up choice” or “don’t you like patients?” It can be a challenge. What’s
your experience been like?
You want to do autopsies, so you want to be a
mortician, right? Not quite. Many times, I’ve been faced with blank stares when
I say I want to be a forensic pathologist. Other times I get the other end of
the spectrum, that’s so cool! Clearly, they’ve seen a few crime-shows and think
that I’ll get to go to crime scenes in stiletto high heeled shoes with a song
by The Who playing in the background as I arrive. Even today when talking with
a dermatopathologist I got a, “well when you realize that hanging out with
dead bodies every day isn’t the greatest, you might consider surg path.”
Then after hearing my experience as an autopsy assistant and that I’m sure this
is what I want to do it was the resigned sigh signalling that I was a lost
A “lost cause,” that’s
frustrating. A lot of specialities rag on other ones, it seems to be part of
the culture of medicine—hopefully not forever, but still can’t we all just get
So, my background
leading to pathology involved me working for several years between college,
graduate school, and medical school; in hospitals of various sizes. I have
personal experiences in these fields and sort of feel “at home” when I’m
dealing with hematopathology, transfusion medicine, cell therapy—that sort of
thing. What piqued your interest in forensics?
I started my undergraduate degree in forensic
biology at the University of Toronto in the fall of 2008 just as a major review
of pediatric forensic pathology in Ontario was being released. After numerous
issues came to light, the inquiry looked at policies, procedures, practices,
accountability and oversight mechanisms, quality control measures and
institutional arrangements within the field in Ontario from 1981 to 2001. Ontario
Court of Appeal’s Honourable Justice Stephen T. Goudge developed 169 recommendations
on how pediatric forensic pathology in Ontario needed to address and correct
its systemic failings to restore public confidence.
After studying the cases that prompted the
inquiry and its recommendations in class, what left the greatest impression was
the importance of having medicolegal autopsies performed by those trained in
not just pathology, but specifically, forensic pathology. What I took away from
the cases of accidental deaths falsely attributed as homicides due to lack of
experience on behalf of the pathologist and other such issues, is that forensic
pathology isn’t something to be dabbled in. While our patients are no longer
alive, there are lives that can be affected by the work we do. In Ontario,
false convictions not only stemmed from “junk science” but also from
inadequacies in the training of pathologists working in a forensic capacity and
also a general shortage of forensic pathologists.
Seems like a lot of us
(of the few of us) who enter medical school knowing we want to go into
pathology have to sort of wait their turn, as it were, collecting experiences
which help make us competitive for residency matching—what keeps your
“commitment algorithm” going?
Since discovering that forensic medicine is a
career path as a high school student, I’ve geared my education towards training
in forensics. First my undergraduate degree and then a side trip for my master’s
degree in Forensic Death Scene Investigation and a job as a pathology
technician at the Medical Examiner’s office on my way to medical school. I have
in each step along the way, confirmed that both medicine and forensics
fascinate me. Scroll through my Netflix account and you’ll find crime dramas
(with the British shows being my favourite) or my podcast app filled with true
crime shows; I am enraptured using science to figure out what happened.
Sidebar: at this point Kyla showed me a first-author published piece in
the Journal of Forensic Sciences from
2017 that talked about law enforcement-involved firearm related deaths in
Oklahoma, where she worked at the time. Basically, it showed through metadata
analysis that gun-related deaths were on the rise. Not just over time, but
number of times being shot. Remember when we talked about pathology’s role in
the #StayInYourLane/#ThisIsOurLane discussion? Well which pathology
speciality do you think works with this stuff directly? Chemistry? Cytology?
Last time I checked GSWs don’t get screened for lead poisoning and you can’t
FNA a bullet. Forensic pathology has often been tasked with seeing trends in
morbidity and mortality and translating that to effective social and public
health change: think seatbelts, stents, and maybe someday gun-related
I was interested when
I shadowed at the Cook County ME’s office a few years ago—I saw some cool
things. I also remember learning a lot from the first real autopsy I saw in a
hospital, ultimately it seems like a totally different field that maybe gets
underappreciated even within the pathology umbrella. AP/CP residents have to do
a certain number of autopsies to graduate, but the attitude I’ve noticed around
the topic is a “necessary evil” and most are working towards not having to do
that. So let me ask you definitively, why forensic pathology?
Medicine is science being applied to find out
what happened in the body and how we can change or manipulate those variables
to diagnose, prevent, treat and manage disease. Each diagnosis is solving a
crime occurring within the cells in the body, if you will. In forensic
medicine, not only do you get to do all that but add in the crime solving
element and you get to be “Dr. Nancy Drew.” While medicolegal systems are
different all over the US and Canada, chances are that as a forensic
pathologist you won’t only be working on your stereotypical
“forensics” cases, the gunshot wounds, stab wounds and other
nefarious causes of deaths many associate with that term. You could get the
generic, “cause of death atherosclerotic cardiovascular disease, manner of
death natural,” for a large proportion of cases.
It’s not glamorous, you could spend your day with a two-week-old decomposing decedent that has a pulsating maggot mass devouring its torso or documenting 51 stab wounds or signing out your cases after reviewing your histology and toxicology reports or testifying on a homicide case you worked on. But for me, those all sound like pretty interesting ways to spend the day, sign me up. As a pathology technician assisting with the autopsies and external exams, I was never required to think about what was happening in the body, but I wanted to understand it all. Now as I progress through medical school and look towards residency and fellowship, I eagerly await the chance to perform my first autopsy as a physician, to put all the knowledge and experience I’ve gained towards helping move Ontario and forensic pathology forward.
I’d like to thank Kyla for her time in talking with me and
her willingness to share her insights with all of you. I wish her all the best
of luck as she continues through her training with electives and core rotations
both in the UK and state-side. If you have any questions to relay to her,
please feel free to comment below and I will forward appropriately. And as
always, don’t forget to share with your colleagues across every discipline!
Thanks for reading, I’ll see you next time where I’ll be
writing from the Mayo Clinic Hospital in Rochester, Minnesota, conducting a
formal rotation in Anatomic and Clinical Pathology! Don’t miss it, I’ll have
lots to share while learning at one of the nation’s top institutions!
Until next time!
–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola
University Chicago with a BS in Molecular Biology and Bioethics and then
Rush University with an MS in Medical Laboratory Science. He is
currently a medical student actively involved in public health and
laboratory medicine, conducting clinicals at Bronx-Care Hospital Center
in New York City.