For most people working in laboratory
medicine, their first encounter with transgender patients likely arose from an
issue involving the Electronic Health Record (HER). For me, I was called into
the reference lab, because an abnormally high estradiol result was found by the
referring lab. They were concerned this might be coming from a hormone
secreting tumor, but inspection of the patient’s record revealed they had been
taking higher than recommended doses of their feminizing hormones.
Today I will share stories from issues
that arise in EMR when gender doesn’t equal sex. While these may not
specifically happen to all of you, I hope they can be informative or help you
anticipate future problems.
Transgender issues came up at one of our
institutions when providers were getting dozens of messages in their in-baskets
about new flagged lab results for multiple patients. This is very annoying,
because they have to address each of these messages or they are out of
compliance with the hospital. An investigation revealed that all of the
patients involved were transgender patients. In order to get estradiol, sold as
oral contraception pills, the pharmacy had to administratively change their sex
in the EHR for approval, then change it back.
This moved their corresponding reference
ranges out of sync, which triggered a new results flag. Changing the sex back
triggered other flags and more messages. This was finally resolved after a
committee was convened and several meetings occurred, but no one would have
anticipated this type of issue arising from a simple action to get patients
Sometimes transgender patients have their
sex changed legally. If an EHR only includes one sex entry instead of gender
and sex assigned at birth, then certain lab errors may prevent processing of
important samples. The pregnancy test for a transgender man could be
auto-rejected. This can be an issue even for providers in front of the patient
as was recently reported in a case to the NEJM about a transman who was
mistaken as obese instead of pregnant and miscarried their child.
Similarly, a prostate biopsy from a
transgender woman could be auto-rejected by a surgical pathology system as an
inappropriate specimen type for the patient. Even further, an EHR could fail to
prompt a provider from making a prostate cancer risk assessment in a
transgender woman, which could result in improper screening.
I would recommend that EHR includes three
separate fields (sex assigned at birth, gender, and legal sex) to fully
recognize transgender patients and provide optimal personalized healthcare to
Gupta S, Imborek KL, Krasowski MD. Challenges in Transgender Healthcare: The Pathology Perspective. Lab Med. 2016 Aug; 47(3):180-188.
Stroumsa D, Roberts EFS, Kinnear H, Harris LH. The Power and Limits of Classification – A 32-YearOld Man with Abdominal Pain. N Engl J Med. 2019 May 16;380(20):1885-1888. doi:10.1056/NEJMp1811491.
-Jeff SoRelle, MD is a Chief Resident of Pathology at the
University of Texas Southwestern Medical Center in Dallas, TX. His
clinical research interests include understanding how the lab intersects
with transgender healthcare and improving genetic variant
A 36 year old female underwent thyroidectomy for multinodular goitre that led to the fortuitous discovery of a neck mass. The neck mass specimen submitted comprised two lymph nodes measuring 2.2 cm and 1.3 cm in the greatest dimensions, with a fleshy tan cut surface.
H&E stained sections revealed numerous non-necrotizing
granulomas effacing and replacing normal lymph node architecture. These
consisted of pale epithelioid histiocytes and Langhans type of giant cells. The
granulomas lacked a peripheral rim of lymphocytes. AFB and GMS stains were
negative for microorganisms
A diagnosis of non-necrotizing granulomatous
lymphadenitis was rendered noting that in the correct clinical context the
findings could represent sarcoidosis.
Granulomatous inflammation is a special type of
chronic inflammatory response characterised by the formation of discrete
collections of histiocytes called granulomas. Activated histiocytes appear as
epithelioid cells with round to oval nuclei, often with irregular contours and
abundant granular eosinophilic cytoplasm with indistinct cell borders. They may
coalesce to form multinucleated giant cells. When found in the lymph node, the
reaction pattern is called granulomatous lymphadenitis. It can be caused by a
variety of different conditions, and therefore, requires thorough workup to
come to a conclusive diagnosis.
On the basis of presence or absence of necrosis,
granulomatous lymphadenitis can be classified as necrotizing or non-necrotizing.
Additionally, the presence of an abscess, usually central, indicates a
Sarcoidosis lymphadenitis is
the prototype of non-necrotizing granulomatous lymphadenitis. It shows the
presence of discrete granulomas without a peripheral rim of lymphocytes, called
“naked granulomas”. The early phase shows follicular hyperplasia and sinus
histiocytosis, followed by appearance of epithelioid cell nodules toward the
end of this phase. The peak phase shows well-demarcated
granulomas composed of epithelioid cells with scattered multinucleated giant
cells observed throughout the lymph node. Granulomas may occasionally coalesce.
In the late phase, increased collagen fibers result in fibrosis and
hyalinization. There are no neutrophils and it is uncommon to find small
foci of central necrosis. Numerous inclusions such as asteroid, Schaumann, or
Hamazaki-Wesenberg bodies can be seen. In this case, we observed
well-demarcated granulomas throughout the lymph node, typical of the peak phase
without any caseous necrosis or suppuration.
Other causes of granulomatous lymphadenitis can be ruled
out as follows.
It shows a similar pattern of non-necrotizing
lymphadenitis like sarcoidosis. However, classically sarcoid like reaction
shows scattered small epithelioid granulomas with sparsely arranged epithelioid
cells. The border of the granulomas is usually obscure. The CD4:CD8 ratio
ranges from 0.8 to 2.25 while in sarcoidosis, it is >3.5. These findings
help distinguish sarcoid-like lymphadenitis from sarcoidosis.
Sarcoid-like adenitis may be seen in numerous conditions
such as carcinoma, Toxoplasmosis, fungal infections, tuberculosis,
immunocompromised states, pneumoconiosis etc. The fact that tuberculosis and
fungal infections can present with a non-necrotizing granulomatous lymphadenitis
highlights the importance of performing fungal (PAS & GMS) and AFB (Ziehl
Neelson) stains in non-necrotizing lymphadenitis as well. In this case, the
granulomas had distinct borders, numerous epithelioid cells, no organisms were
identified on special stains, nor was there any history of immune compromise;
ruling out a sarcoid-like reaction.
Berylliosis: The lymph node picture in Berylliosis is identical to that of sarcoidosis.
We may even see asteroid bodies or Schaumann bodies. A diagnosis can be
established by eliciting a history of chronic exposure to Beryllium. Beryllium
lymphocyte proliferation test (BeLPT) is a test that measures Beryllium
sensitization and is very specific for Beryllium exposure. There was no known
history of exposure to Beryllium in this case.
Toxoplasmosis: A classic triad of follicular hyperplasia, small granulomas composed of epithelioid cells within and around hyperplastic follicles and, monocytoid B cell hyperplasia, is observed in toxoplasmosis lymphadenitis. This case did not show follicular hyperplasia, ruling out toxoplasmosis.
Necrotizing granulomatous lymphadenitis
Even though we did not find any necrosis in this case,
yet, it is worthwhile to review briefly the various causes of necrotizing lymphadenitis.
of a tuberculous lymph node is characterised by central caseous necrosis
surrounded by an epithelioid cell layer. The outermost layer is comprised of
lymphocytes and fibrosis. Plasma cells are not observed. Diagnosis can be
established by performing an AFB stain that demonstrates acid fast rod shaped
bacteria in the areas of necrosis. Organisms can also be detected by PCR.
About 0.7 to 2.3% of BCG vaccinated children may develop BCG lymphadenitis that
is smaller than tuberculous lymphadenitis. Early phase shows follicular
hyperplasia and sinus histiocytosis. Later, there is development of
micronodules of epithelioid granulomas without necrosis and epithelioid cell
granulomas with central caseous necrosis. Langhans giant cells are rare.
Fungal infections by Histoplasma, Cryptococcus, coccidiodomycosis, pneumocystis
may also cause a necrotizing granulomatous inflammation. There are numerous
neutrophils, and fungal structures can be seen. GMS and PAS can be used in
cases where it is difficult to the find the fungal elements on H&E.
are three forms of histological changes, Abscess form, showing abscess
with central necrosis and mononuclear cells, Abscess-granulomatous form with granulomas with central necrosis,
which form large lesions with central abscesses, and granulomatous form with
caseating necrosis at the centre of the granulomas.
Cat Scratch disease:
Similar to tularemia, there are three phases of histologic presentation, an
early phase of follicular hyperplasia, intermediate phase of microabscess, and
a late phase of granulomatous inflammation. Monocytoid B cell clusters are
observed close to the abscess.
Sarcoidosis is usually diagnosed by
excluding other causes of granulomatous inflammation, as we did in this case.
Characteristic non-necrotizing, discrete granulomas were seen throughout the
lymph node. The age of the patient and female gender epidemiologically support
the diagnosis. This case reflects an example work up of a granulomatous
lymphadenitis that is a morphologic presentation of myriad diseases.
-Swati Bhardwaj, MD has a special interest in surgical pathology and hematopathology. Follow her on Twitter at @Bhardwaj_swat.
–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.
Kumarasen Cooper, MD, PhD completed his medical training
from his home country in South Africa and his PhD at Oxford. He now works as a
surgical pathologist at the University of Pennsylvania and is responsible for
leading the initiative to engage the pathology department in the Botswana-UPenn
partnership through the Perelman School of Medicine Center for Global Health. He
has over 260 publications and has lectured in 5 continents. Despite this busy
schedule, Dr. Cooper devotes two separate months of the year to work in
Botswana’s only academic pathology department, where he pours his energy into
helping the department advance.
I met Dr. Cooper through email when I heard about the work
he was doing in Africa. He generously agreed to come visit my department to
give an excellent Grand Rounds lecture on his experiences working in Global
Pathology, and he led a much-appreciated resident slide session of unusual and
difficult cases from his work in Botswana. Humility and grace envelop Dr.
Cooper despite his brilliant accomplishments. He also proved to be incredibly
generous with a refusal of his speaker honorarium, in exchange for an agreement
that we would collect pathology textbooks to send to the under-supplied
residency program in Botswana. I’m excited to share the inspiring work that he
does through the Botswana-UPenn partnership with all of you today, as I think
this program could be used as a model for all institutes to involve their
pathology departments in global health opportunities.
Q: What began your interest
in global health?
A: I was born,
raised, and completed my medical training in South Africa. I spent 15 years
working as a Pathologist and served as the Chair of Pathology in Johannesburg
until I was recruited to the US to work as Vice-Chair at the University of
Vermont. I knew when I left Africa that I would always come back, and that I
could use what I learned abroad to give back in some way. I wasn’t sure in what
form that would take at the time, but I knew there was work that still needed
to be done. This was also influenced by my visits to the pathology departments
in many different countries over the years…I was able to gain a sense of the
‘haves and have-nots’, and so developed a strong feeling that I needed to give
A: When I first discovered
the partnership, I thought that this may be an avenue for me to participate in
global pathology. At the time, the pathology department was not involved in any
of the ongoing BUP projects, though other clinical departments at UPenn were. After
my initial assessment of the Botswana pathology department and its resources in
April of 2016, I was able to identify ways that I could help. Together with the
Director of BUP, I approached the Chairman of my department with the proposal,
and we started the pathology partnership program in October of that year. Since
then, I travel to Botswana twice a year for one month at a time, and each time
I take 1-2 residents from UPenn along with me.
Q: Can you describe
the pathology department in Botswana?
A: To serve a
population of just over 2 million people, Botswana has only one academic
pathology department, a College of the University of Botswana (UB) School of
Medicine, which consists of six pathologists who
are all from other countries. There are currently no Botswana pathologists
working in the department. There are about six technicians working in the
laboratory, all of whom were trained internationally. The laboratory receives
around 7,000 surgical specimens yearly, plus cytology, and autopsy. They work
with an extremely limited panel of immunostains that are not routinely used but
are spared for the rare case that cannot be diagnosed with morphology alone.
The residency program is still very new. There are six
residents in the program at the present time, and the program is designed so
that they will spend the first two years in Botswana and then they will
continue their final years of training in South Africa. I look forward with
anticipation to the first Botswana trained pathologists in the country.
Q: What is your role
when visiting Botswana?
A: We try to help
with everything we can. I sign out cases with the residents during the time I
am there, and I teach the residents using these cases every day. The UPenn
residents that I bring with me are eager to teach as well, so they deliver
didactics regularly also. We all participate in tumor boards and the FNA
clinic. We each take on projects that we can partner with them to tackle…things
like improving turnaround time, quality improvement, and SOP preparations. We also work on developing academic programs, grossing
templates and manuals (A UPenn pathology PA spent two weeks working in Botswana
on this project), synoptic reports, cancer guidelines…anything they need I try
to help them with.
Q: How are the UPenn pathology
residents given credit in their home program to join you?
A: As of this
year, the BUP pathology program is now offered as one of the official electives
that residents are allowed to choose from. They are able to use elective time
and their travel expenses are paid for by a resident travel grant.
Q: In your role as
supervisor of the UPenn residents, what do you see the residents gaining from
A: The residents
that have come with me to Botswana are very compassionate and are eager to
contribute in any way they can. Experiencing pathology in Botswana, where
people are trying to achieve so much with so little resources, it makes the
UPenn residents even more grateful for all of the resources they have available
to them. They also have the opportunity to not only learn from the unusual
cases that present in Botswana, but also the opportunity to contribute their
own unique set of skills – some have focused on teaching autopsy technique,
others give enthusiastic and detailed
lectures, and one gave a talk about successful study techniques. [For more
information about the resident experience, one can read more about it in the UPenn
blog here: https://pathology.med.upenn.edu/department/blogs/residency-matters/penns-pathology-residency-program-reaches-botswana]
Q: How do you see the
BUP pathology partnership affecting the trainees in Botswana? What changes have
you seen since you started working with them?
A: The residents in
Botswana really appreciate the partnership that we have formed. I have seen the residents develop so much
since working with them. At first, they were reserved and now they actually
request lectures on topics they feel they could improve on. They are still very
humble and respectful, but I have encouraged them to be advocates for
themselves. They have really embraced their program and I’m very proud of them.
We have a deep appreciation for each other and are proud of what we have
We’ve also started hosting Botswana residents at UPenn for a
one month rotation so they have the opportunity to supplement their training
even further. We fly them to the US, house them, and include them in our
residency training program for the month. They have the opportunity to sit in
on sign-outs, shadow grossing and autopsy, attend conferences, and be exposed
to the advanced testing that we routinely perform in the US.
Q: How do you see the
pathology partnership growing in years to come?A: I’m currently helping them find placements in
South Africa or possibly partnering with private laboratories to help expose
the residents to a greater diversity and volume of cases. As the program
continues to grow, we look forward to seeing the fruits of the partnership for
many years to come.
-Dana Razzano, MD is a Chief Resident in her third year in
anatomic and clinical pathology at New York Medical College at
Westchester Medical Center and will be starting her fellowship in
Cytopathology at Yale University in 2020. She was a top 5 honoree in
ASCP’s Forty Under 40 2018 and was named to The Pathologist’s Power List
of 2018. Follow Dr. Razzano on twitter @Dr_DR_Cells.
The patient is a 43 year old woman who experienced chest congestion and presented to her local physicians office. A chest X-ray was ordered and demonstrated a lung abnormality. A follow-up CT scan confirmed a 1.9 cm smoothly marginated nodule in the upper lobe with no adenopathy and a normal liver and adrenal glands. The nodule was mildly hypermetabolic on PET scan. A bronchoscopy was performed, which was non-diagnostic. Two subsequent CT scans demonstrated no change in the size of the nodule. Overall, the patient feels well and denies cough, hemoptysis, dyspnea on exertion, and weight loss. Due to the suspicion of cancer, the patient has decided to undergo a lung lobectomy.
Received in the Surgical Pathology lab for
intraoperative consultation is a 30.0 x 7.2 x 2.2 cm lung lobectomy specimen. There
is an attached 6.2 cm staple line, which is removed and the subjacent resection
margin is inked blue. The entire pleural surface is inked black. The specimen
is sectioned revealing a 2.1 x 1.7 x 1.0 cm white-tan, firm, round nodule that
is 0.5 cm from the blue inked resection margin and 0.2 cm from the black inked
pleural surface. The remainder of the specimen is composed of red-tan, spongy,
grossly unremarkable lung parenchyma without nodules or other lesions.
Photographs of the specimen are taken (Figure 1). A representative section of
the nodule is submitted for frozen section and read out as “diagnosis
deferred”. Representative sections of the specimen are submitted as follows:
Nodule, entirely submitted
A8-A10: Grossly unremarkable lung parenchyma
Immunohistochemical stains show the epithelial cells in the lesion to be positive for CK7, TTF-1, and surfactant proteins A and B which supports these cells to be type 2 pneumocytes (all controls are appropriate). Based on the immunohistochemical stains and routine H&E slides, the case was signed out as a sclerosing pneumocytoma
Sclerosing pneumocytoma (SP) is a rare, benign pulmonary
tumor that was first described in 1956 as a vascular tumor, but has since been
found to be of primitive respiratory epithelium origin. In the past, SP has
also been referred to as sclerosing hemangioma, pneumocytoma, and papillary
pneumocytoma, but the 2015 World Health Organization classification of lung
tumors states that the agreed upon term for this tumor should be a sclerosing
pneumocytoma. SP is commonly seen in middle aged adults, with a female to male
ratio of 5:1. There is no racial bias. Patients are usually asymptomatic, with
the tumor incidentally found on screening chest radiographs. If the patient was
to present with any symptoms, they would usually include a cough, hemoptysis
and chest pain. Radiographically, SP appears as a solitary, well-defined,
homogenous nodule along the periphery of the lung.
Grossly, most SPs appear as a solitary, firm, well-circumscribed,
yellow-tan mass generally arising along the periphery of the lung. The majority
of these tumors appear within the lung parenchyma, but there have been cases
reported of endobronchial and pleural based SP tumors. Multifocal unilateral
tumors and bilateral tumors are uncommon.
Histologically, SP consists of two epithelial cell types:
surface cells and round cells. Surface cells are cuboidal, resembling type II
pneumocytes, with finely stippled nuclear chromatin, indistinct nuclei,
occasional nuclear grooves, and inclusions. The stromal round cells will have bland
oval nuclei with coarse chromatin and eosinophilic cytoplasm (Figure 2). Both
the surface cells and round cells will have a low mitotic rate, but can have
moderate to marked nuclear atypia. Ciliated bronchial epithelium is often
identified in the tumor. There are four architectural patterns identified
within SP: papillary, sclerotic, solid and hemorrhagic, with over 90% of SPs
displaying three of the patterns, and all of the tumors containing at least two
of the patterns.
Papillary pattern: Complex papillae composed of surface cells covering a stroma of round cells
Sclerotic pattern: Papillae containing hyalinized collagen, either in solid areas or along the periphery of hemorrhagic areas (Figure 3)
Solid pattern: Sheets of round cells bordered by surface cells
Hemorrhagic pattern: Large blood filled spaces
Immunohistochemical stains can be helpful in the diagnosis of
SP, with both the surface cells and round cells exhibiting expression of
thyroid transcription factor 1 (TTF-1) and epithelial membrane antigen (EMA). It
should be noted that TTF-1 is also used for the diagnosis of pulmonary
adenocarcinoma, increasing the risk of misdiagnosing SP. The surface cells will
also express both pancytokeratin (AE1/AE3) and Napsin A, with the round cells
being negative for AE1/AE3, but having a variable expression of cytokeratin 7
and the low molecular weight cytokeratin (CAM 5.2). Molecular pathology has demonstrated
a frequent loss of heterozygosity at 5q, 10q and 9p, and an allelic loses at
p16 in the surface and rounds cells. Although the immunohistochemical stains
and molecular pathology results can be very helpful, diagnosis of a SP is still
largely based on routine H&E slides showing the two epithelial cell types
and four architectural patterns.
Electron microscopy will show abundant lamellar bodies
similar to those in type II pneumocytes in the surface cells. Round cells will
lack the lamellar bodies and instead will contain variably-sized electron-dense
bodies that have been thought to represent the different stages of lamellar
The differential diagnosis for SP includes a variety of
benign and malignant neoplasms, which can be difficult to distinguish on
cytology, small biopsies and intraoperative consultations. The cytologic
features include moderate to high cellularity with a bloody background and
foamy macrophages, occasional nuclear pleomorphism in the round cells, absent
mitotic figures, and occasional necrosis with cholesterol clefts and
calcifications. In the case of small biopsies, making a diagnosis of SP can be
difficult if the papillary pattern is highly prevalent without one of the other
three patterns present. With intraoperative consultations, the frozen section
artifact can make it difficult to appreciate the two epithelial cell types or
the four architectural patterns. The gross examination, as well as the
radiographic findings of a well-circumscribed tumor can help point the
Pathologist to favoring a benign neoplasm over a malignant one. The benign
neoplasms that should be considered in the differential diagnosis include:
Clear cell tumor, which will have clear cells
with scant stroma, thin-walled vessels and a strong expression of HMB-45
Pulmonary hamartoma, which will have a
combination of cartilage, myxoid stroma, adipose tissue and trapped respiratory
Hemangiomas, which are rare in the lung, and will
lack epithelial cells and contain either a cavernous or capillary morphology
The malignant neoplasms that should be considered in the
differential diagnosis include:
Bronchioalveolar carcinoma, which can have a
papillary pattern, but will not contain the two epithelial cell types and
combination of the four architectural patterns
Metastatic papillary thyroid carcinoma, which is
distinguished from SP by the presence of the characteristic Orphan Annie nuclei
Metastatic renal cell carcinoma, which will
contain nuclear atypia and striking vascularity
Carcinoid, which will contain organoid and
ribbon-like growth patterns
Currently, with the benign nature of SP, surgical excision is
the preferred treatment choice to cure the patient. There have been cases
reported of lymph node metastasis and recurrence, but neither of these appear
to effect the prognosis. This just helps to highlight the need for a
multidisciplinary approach to this benign tumor.
Hisson E, Rao R. Pneumocytoma (sclerosing
hemangioma), a Potential Pitfall. Diagn
Keylock JB, Galvin JR, Franks TJ. Sclerosing
Hemangioma of the Lung. Arch Pathol Lab
Travis WD, Brambilla E, Nicholson AG, et al. The
2015 World Health Organization Classification of Lung Tumors: Impact of
Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243-1260.
-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
Last month, it was as fun to write about hematology peripheral
smear differentials as it was to address the importance of
interdisciplinary collaboration. I found myself in a unique position both as a
medical student as well as a former medical laboratory scientist in what was a
great clinical training rotation in hematology/oncology. Now, with just one
rotation left until the end of my medical school journey, I want to take you on
a look back at some of the very first posts I made here on Lablogatory and
update you on the intersectional, collaborative topic that I shared with you
almost two years ago: Zika!
In a recent digital article on ASCP’s partner, The
Pathologist, author and staff editor Michael Schubert wrote about the
connectivity between public health, epidemiologic research, laboratory
medicine, and clinical patient outcomes. He examined the effectiveness and
accuracy of Zika testing availability in commercially available assays and
spoke with a leading virologist in the field from Berlin. You may recall one of
those “ancient” posts I made about Zika, where I was part of a research team
that used the same methodology! Combined immunoglobulin-specific assays,
arbovirus detection in the heat of a public health epidemic’s epicenter, and
lab medicine that complimented my concurrent immunology class in med
school—what more could you ask for?
And, since the last tagged Lablogatory Zika update I can see
by Dr. Sarah Riley in February of 2017, here’s my update! Dr. Riley’s post
was a fantastic summary of the Zika epidemic, its troublesome diagnostic
assessments, and the recommendations and plans of organizations like the World
Health Organization (WHO). She was, and still is, right—the “struggle is still
real’ when it comes to Zika testing. Curious about what it was like during the
2016 epidemic? Who was doing testing, what kind of testing, and what was the
lab data climate? Well…it feels like it’s time for a…
*** FLASHBACK ***
An Arbovirus Abroad
Hey! My inaugural
post! It was fun to go back and see the data from the work then (Spoilers:
epidemiologic updates are on your horizon). We were just getting started to
take an assessment of the situation and address it as a public health concern.
My then Caribbean location was a great place to study Zika trends coming from
Brazil, Puerto Rico, and Florida. As a snapshot, at that time (Dec 2016) there
were a purported almost 2,000 cases, however less than a fifth of those cases
were serologically confirmed by lab testing. Before the recommendations to move
toward RT-PCR, most labs in the region were requesting commercially available
screening tests for IgG/IgM assays.
How do you reach people when you’ve got compelling public health
lab data that translates to possible prevention of infection and spread of
disease? Easy: go
to where the people are and engage them when and where they’re comfortable.
One of the overarching themes in public health is mitigating barriers to change
by way of utilizing social humility. This a certainly a type of
interdisciplinary collaboration because if we’re the experts on IgM and IgG
trends in testing confirmations, the public are the experts in social
determinants of health within their communities.
Laboratory Data and Global Health Security
As my team and I were busy preparing SOPs, conducting a new
project aimed at improving local health literacy and source reduction, securing
IRB approval, and collecting data about the residents of Sint Maarten to
correlate with local Health Ministry projections, one of the officials—who now
serves as a regional director for PAHO—took our work to the Global
Health Security Agenda Summit. Talk about motivation! In and out of the
lab, I worked with teams who were getting some fantastic work done on the
ground with respect to mosquito-borne virus research.
IRBs and Public Heath Pathology
For those of us who work in laboratory medicine, it’s easy
to talk about the best way to test, detect, and treat an epidemiologic
threat—it’s even exciting when it’s a current threat. But to really be
successful, you’ve got to collaborate with those outside of the lab, and often
this means thinking “outside the box.” Public
health is different from lab medicine in that while lab-work is based
around results, testing, and organized data-driven decisions, success in public
health is highly determined by community buy-in in the form of partnerships!
*** FLASH …
So, after my time in Sint Maarten, I came to New York City
to rotate through my clinical clerkships. And, if you’ve seen some more recent
post-Zika posts on this website, you know they’ve been going great! Within a
few months of being here, my wife brought back some swag from a training
session she attended. (Side note: she’s a graduate-level nurse, working in the
public health non-profit sector with vulnerable populations in the inner
city—she’s too busy to blog.) After months of both of us working and learning
about Zika and public health initiatives in the Caribbean, we were greeted by
this fantastic toolkit from the New York State Department of Public Health!
The take home message: collaboration is key, both inside and
out of the lab. Schubert’s piece in The Pathologist created a fantastic
dialogue in addressing the clinical needs for interdisciplinary collaboration.
The best testing means finding out exactly where the needs are and using
data-driven decisions to implement change or action. In the lab, that means
constantly working for higher quality and better patient outcomes in every
test, result, report, and (mosquito) byte of data. In the field, it means the
same thing, but instead of metrics like sensitivity, specificity, and TAT it’s
about cultural humility, attainable goals, and dynamic timing.
Thanks for reading! Hope most of our national heat wave spared you, but if it didn’t remember: don’t keep standing water around, wear light loose clothing, and use appropriate insect repellent!
See you 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.
who works in a laboratory knows that there are certain rules and regulations to
be followed to ensure accuracy in testing, and the safety of both the patient
and testing personnel. With all the acronyms floating around (CLIA, FDA, CAP,
CMS, TJC) it can get confusing to keep track of who controls what, and which
rules apply to your specific lab. In the first installment of this 3-part
series on regulations, we’ll review the different federal agencies responsible
for oversight and moderation of the laboratory. In part 2 we’ll go further
in-depth to demystify testing complexity (waived, non-waived, PPM) and why it’s
important to know the correct classification for the tests you perform. Lastly,
we’ll review the optional accreditations available to labs, and how
accreditation differs from certification.
refers to the Clinical Laboratory Improvement Amendments of 1988. These
amendments were drafted to the Public Health Services Act, in which the federal
program was revised to include certification and oversight of clinical
laboratory testing. Although there have been two additional amendments made
after 1988 (1997, 2012), the law still continues to be cited as CLIA ’88 as it
is named within legislation.
CLIA regulations helped to establish quality standards for all U.S. laboratory
testing performed on human specimens (except for research) for the purpose of
assessment of health, or the diagnosis, prevention, or treatment of disease.
The regulations cover all aspects of testing including general laboratory
requirements, quality monitors, pre-analytics, analytic performance,
post-analytics, and personnel requirements.
addition to setting the basic ground rules for performing quality laboratory
testing, the CLIA regulations also require clinical laboratories to be
certified by their state as well as the Center for Medicare & Medicaid
Services (CMS) before accepting human samples for diagnostic testing.
Laboratories can obtain multiple types of CLIA certificates, based on the kinds
of diagnostic tests they perform. In order for laboratories to receive payments
from Medicare or Medicaid, laboratories must be properly certified for the
testing they are performing and billing for.
3 federal agencies responsible for enforcing the CLIA regulations: The Food
& Drug Administration (FDA), Center for Medicaid Services (CMS) and the
Center for Disease Control and Prevention (CDC). Each agency has a unique role
in assuring quality laboratory testing.
Centers for Medicare & Medicaid Services (CMS) is the federal agency
responsible for ensuring that the CLIA standards are upheld and enforced. Their
responsibilities include the following:
inspections and enforcing regulatory compliance
private accreditation organizations (such as CAP) for performing inspections,
and approves state exemptions
laboratory performance on Proficiency Testing (PT) and approving PT programs
CLIA rules and regulations
& Drug Administration (FDA) is primarily responsible for reviewing and
approving new tests, instruments, and equipment used in diagnostic laboratories.
They also perform the following tasks:
tests based on complexity
requests for Waiver by Application from manufacturers
rules/guidance for CLIA complexity categorization
for Disease Control and Prevention (CDC) responsibilities include the following
analysis, research, and technical assistance
technical standards and laboratory practice guidelines, including standards and
guidelines for cytology
laboratory quality improvement studies
proficiency testing practices
and distribute professional information and educational resources
the Clinical Laboratory Improvement Advisory Committee (CLIAC)
summarize, CLIA establishes the rules and guidelines that laboratories must
follow to ensure they are providing accurate laboratory results. Federal
agencies then work together to support the CLIA amendments and enforce
compliance. All certified laboratories will be subject to inspection by
regulatory agencies to ensure compliance with the rules. In some cases, your
local state Department of Health (DOH) or accrediting agency may be more
stringent or have additional requirements to be followed – always go with the
stricter requirement to ensure compliance with all agencies.
up next we’ll review how the FDA decides the complexity of each test, and how
this designation will affect the CLIA rules to be followed.
-Kyle Nevins, MS, MLS(ASCP)CM is one of ASCP’s
2018 Top 5 in the 40 Under Forty recognition program. She has worked in
the medical laboratory profession for over 18 years. In her current
position, she transitions between performing laboratory audits across
the entire Northwell Health System on Long Island, NY, consulting for
at-risk laboratories outside of Northwell Health, bringing laboratories
up to regulatory standards, and acting as supervisor and mentor in labs
with management gaps.
Large biological and chemical spills are not a common
occurrence in the laboratory. That’s a good thing, but when they do occur, they
can create a very dangerous situation. It is vital that lab staff know how to handle
such events even though they may not be commonplace.
Some laboratories differentiate between large and small
spills. They may have an emergency number to call for a hazardous spill
response team. Other smaller facilities simply don’t have that in place. Either
way, it’s important for laboratory professionals to know they are the experts
about the biological and chemical materials they use, and they need to be in
charge as the experts when a spill situation needs to be managed.
Most laboratory spills can be managed using a standardized step-wise
process known as the S.P.I.L.L.E.D. procedure. I don’t usually ask lab staff to
memorize the acronym, but having the information contained on a poster with the
lab spill kits can make a clean-up procedure go smoothly.
S = Secure the Site – Make sure no one walks through the
area where a spill has occurred. It could be a dangerous situation if a
hazardous chemical is spilled, and you would never want someone slipping in the
area or tracking the spilled material to another area.
P = Protect Yourself – Arm yourself with the
appropriate Personal Protective Equipment (PPE). In a lab spill event, this
would mean using a lab coat, gloves, and face protection to prevent accidental splashes.
I = Inspect the Spill – Look to see what was spilled.
If it is a hazardous chemical, is there a concern about fumes? Obtain a Safety
Data Sheet to see if section 6 will give any special information about handling
the accidental release or spill of that chemical. Consider other spill concerns
such as broken glass or possible ignition sources if flammable material is
L = Lay Down a Barrier – If the spill is large and
spreading, lay down spill pillows or booms designed to contain a flow of
liquids. Surround the spill area with these materials. Sometimes, the use of an
emergency shower can create the need for a barrier to be made.
L = Lay Down Absorbents – No matter the size of the spill,
the next step is to place any absorbent powders, granules or clean-up pads to
soak up the spilled material. If the absorbent is also a neutralizer, make sure
you allow the necessary time for neutralization to occur.
E = Extract the Mess – Use implements to pick up the
materials used for stopping and absorbing the spill.
D = Dispose of the Waste – Properly dispose of all
materials involved with the spill clean-up. If there was glass involved, be sure
to use a sharps container. Biohazard
material should go into an appropriate container, and chemical waste materials
may need to be disposed of separately for pick-up by a chemical waste vendor.
Lab staff should be able to access spill control materials
quickly, and the necessary items should be stored in a location designated by
signage. Perform an inventory of spill supplies and make sure there are
adequate materials that could handle spills of the biohazards and chemicals stored
and used in the department. Be sure items in the spill kit are not expired, and
if there is no expiration date for absorbent powders, check them at least
annually for effectiveness.
All laboratory staff need to have complete spill clean-up
training. Give information about the types and locations of spill kits and how
to handle various types of spills that can occur. Once that training is done,
it will become important to perform spill drills in the department. Drills can
be performed a number of different ways, but a common method involves having a “victim”
spill water onto the floor and claim the material splashed into their eyes.
Watch from a distance to see how the staff reacts. Do they provide appropriate
first aid? Do they inspect the container label? Do they access the correct
clean-up supplies and facilitate cleaning efficiently? Make notes of how the
drill went, discuss them with the staff, and repeat the drills until all staff
are comfortable with a spill situation.
and chemical spills should not be a common occurrence in the lab. When they do
occur, however, the situation can become serious quickly, and a fast and effective
clean-up needs to occur. Because these events are rare, it becomes important to
provide regular spill training and drills so staff can remain ever-ready to
–Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years
experience as a certified medical technologist. Today he is the
Laboratory Safety Officer for Sentara Healthcare, a system of seven
hospitals and over 20 laboratories and draw sites in the Tidewater area
of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.