The Basics of Deaths by Fire: Answering Your Burning Questions

Emergency services were called to a fire in a small apartment building, in which the structure was completely engulfed. Most of the occupants had been evacuated – however, once the fire was extinguished, the charred remains of an adult woman were found in the debris.

At the autopsy of severely fire-damaged human remains, two key questions must be answered: 1) who is the decedent?, and 2) were they alive when the fire started?

Question #1 is particularly relevant in this case, as many people lived in the building. Presumptive identification based on the tenant list may seem reasonable at first, but this victim could represent a visitor, contractor, or subletter. When facial identification isn’t possible, radiographic identification can be done with dental x-rays or x-rays of other bones which may have unique features from healed trauma or degeneration. Additional methods of positive identification could include fingerprints (if still intact), or DNA comparison to first degree relatives.

Question #2 is of importance because fire can be used in an attempt to disguise the identity of a victim of violent crime and destroy evidence. Cutaneous evidence of trauma may be disguised by burns, so full body x-rays are taken of every fire-damaged body. X-rays can also reveal retained bullets, knife tips, or fractures unlikely to have been caused by the fire.

When deciding if a fire victim was alive when the fire started, we first examine the upper and lower airways for soot.  Most fire victims do not die from cutaneous burns, but from smoke inhalation – including carbon monoxide (CO) toxicity, which is often apparent by cherry red discoloration of the blood and viscera. Postmortem carboxyhemoglobin measurements in house fire victims are typically greater than 50%. There are exceptions to this rule, of course. Rarely, someone who was clearly alive when the fire began will have minimal or no soot in their airways and a negligible carbon monoxide concentration. This can happen in a “flash fire”, such as one ignited by gasoline or oxygen tanks, in which thermal injury to the upper airway may cause rapid occlusion by laryngospasm or edema. People with underlying heart or lung conditions will be more susceptible to the effects of carboxyhemoglobin, and may not survive long enough to obtain a level above 50%. Fires also produce other toxic products of combustion such as cyanide, and can lower ambient oxygen saturations to result in asphyxiation by lack of ambient oxygen (even without CO).

Forensic pathologists need to be aware of the artifacts that fires can create. Pugilistic posturing of fire victims (limb flexion) is due to heat-related contraction of muscle fibers. Epidural hematomas can result from boiling blood and bone marrow within the calvarium extravasating into the epidural space. The heat can induce fractures in exposed bone once the surrounding soft tissue is consumed or fully charred. Finally, the heat can split apart skin and soft tissue, resulting in sharp-force-like defects which occur parallel to the orientation of muscle fibers (rather than across them, which is more suspicious for penetrating trauma).

Of utmost importance in fire-related deaths, however, is scene investigation. The manner of death in fire fatalities is related to the origin of the fire. Most fire deaths are accidental, as the fire is unintentionally sparked by some electrical malfunction or unattended flame. However if the fire started intentionally, the manner of death can be homicide (if started by another) or suicide (started by the victim). It is therefore crucial to review the final fire investigation report before finalizing the autopsy report and death certificate. 

This image shows dark black soot lining the main and lobar bronchi; this indicates the victim was breathing during the fire.
Heat-related epidural hematomas have a brown, amorphous appearance rather than the bright red color of traumatic epidural hematomas.
The scalp has been consumed by fire, and the exposed bone is calcined and brittle with fractures of the outer table.

-Alison Krywanczyk, MD, FASCP, is currently a Deputy Medical Examiner at the Cuyahoga County Medical Examiner’s Office.

Determining Time of Death: Separating Science from Pseudoscience

One of the most common questions I’m asked by family members is “do you know when they died?” If death occurs in the hospital, or is witnessed, the time of death isn’t controversial. It’s common though in forensics that people may not be found for hours, days, weeks, or more. Forensics television shows usually depict an investigator measuring body temperature at the scene, and then confidently declaring they’ve been dead for 44 hours. Unfortunately, there aren’t any existing methods that actually give that level of precision – but there is a way we can systematically approach the question.

When determining time of death (TOD), it’s most important to keep in mind that it will be an estimate. The estimate starts with the “window of death” – the time between when the decedent was last known alive and when their body was found. The smaller this window, the greater accuracy is possible.

Once the window is known, one can assess postmortem changes of the body. Livor mortis is the gravity-dependent settling of blood within vessels, which can appear as soon as twenty minutes after death. Sparing of lividity will be present in areas of pressure, such as parts of the body pressed against the floor or with tight clothing. Livor is initially blanchable, but after 8 to 12 hours blood extravasates from vessels and it becomes “fixed”. Clearly though, this only allows one to differentiate between ‘less than’ or ‘greater than’ 8 to 12 hours.

Rigor mortis (stiffening of the body after death) occurs because of postmortem ATP depletion. Muscle fibers require a supply of ATP to both contract and relax – once ATP levels are sufficiently low, muscle will remain contracted until the fibers are broken down by decompositional changes. Generally speaking, rigor starts to develop within an hour of death, peaks from 12 to 24 hours, and dissipates by 36 hours. However, these are average intervals. The onset of rigor is hastened by vigorous physical activity, seizures, electrocution, or increased body temperature, which preemptively deplete ATP. Rigor is also harder to detect in people with low muscle mass (e.g. infants), and can’t be assessed in frozen bodies with those with extensive thermal damage.

Cooling of the body after death, known as algor mortis, is similarly prone to interfering elements. One can find many formulas for estimating the time of death based on the temperature of the body – unfortunately, none of them are particularly useful because of the assumptions that must be made. Change in temperature after death is affected by numerous variables, including body habitus, clothing, wind, actual body temperature at the time of death (not many people are constantly at 98.6℉), sepsis, terminal seizures, and many others. If the environment is warmer than the body, the temperature can even increase after death.

I’ll briefly mention vitreous potassium measurement, which is probably the most recently discovered (and debunked) “holy grail” of time of death. Similar to algor and rigor mortis, vitreous potassium does a reasonably decent job predicting time of death in a controlled experiment – but in this line of work, people don’t tend to die in controlled environments.

At the end of the day, time of death is best estimated by thorough scene investigation, correlated with the evidence the body provides. Newspapers or mail not retrieved from the mailbox, expiration dates on perishable groceries, last refills of prescriptions, and unreturned text messages or phone calls can all narrow down the window of death.

As stated earlier, the longer the interval between death and discovery of the body, the more difficult time of death determination becomes. In advanced decomposition, there is no rigor, livor, or algor remaining to assess (there may even be scant residual soft tissue). In one such situation, despite months of a potential “window of death”, dates on unopened bills and crossed-off calendar dates helped us place the time of death within one or two days. It’s not as flashy as multivariate equations for temperature or potassium levels, but it’s far more accurate and scientifically defensible.

Image 1. The quilting pattern of this decedent’s mattress is visible in the livor mortis on his back.
Image 2. This decedent’s right arm is defying gravity due to rigor – he was initially face down, and his arm musculature became temporarily fixed in this position. Rigor can be forcibly broken if needed, but will also break down as decomposition proceeds.

-Alison Krywanczyk, MD, FASCP, is currently a Deputy Medical Examiner at the Cuyahoga County Medical Examiner’s Office.

Dying in a Winter Wonderland: Staying Safe as the Temperature Drops

A 40 year old man was found deceased in a parking garage in a Midwest city. It was late October and had rained the previous evening. He was identified by his sister who was a tenant in the adjacent apartment building. Unknown to her, he had recently been discharged from the hospital after a one-week psychiatric admission. His sister stated he was homeless and would occasionally sleep in the parking garage for shelter.

At the scene the decedent was prone on the ground, clad only in a pair of boxers. His water-soaked shoes, socks, sweatpants, and shirt were strewn about him. Autopsy revealed an atraumatic, thin adult man. Prominent pink discoloration was noted over the hips and knees. Internal examination showed only patchy black-brown discoloration of the gastric mucosa and pale kidneys. Histology was remarkable for subnuclear vacuolization of the renal tubular epithelium. The cause of death was certified as environmental hypothermia, and the manner of death accidental.

Hypothermia is defined as a core body temperature below 95℉ (35℃) and can result from endogenous illnesses like hypothyroidism or sepsis. The most common cause, though, is exposure to cold environments. On exposure, the hypothalamus initiates shivering and increases cellular metabolism to produce heat. Another crucial survival response is vasoconstriction, particularly of vessels in skin and skeletal muscle. If the overall loss of heat overtakes the body’s ability to produce or retain heat, hypothermia will result.

Developing hypothermia doesn’t require frigid weather – in dry air, temperatures of 50℉ can still result in hypothermia. Wind removes warmed air surrounding the body, and water conducts heat three times faster than air; therefore, with either of these factors present, people can develop hypothermia at even warmer temperatures,

The autopsy findings of hypothermia are not specific. External examination may show bright pink discoloration of the skin over joints (“frost erythema”). There may be black-brown spots on the gastric mucosa, (“Wischnewsky spots”), thought to result from terminal vasodilation of submucosal vessels. The kidneys may be pale with microscopic subnuclear vacuolization of the tubular epithelium (the “Armanni-Ebstein” lesion). Acute hemorrhagic pancreatitis has also been described. However, these findings require a period of survival to develop—many cases, particularly if the decedent succumbs quickly, show no findings at all. The diagnosis of hypothermia therefore relies heavily on scene investigation. “Paradoxical undressing” (demonstrated in this case), refers to the phenomenon of a terminally hypothermic person taking off their clothes. This is caused by a feeling of warmth resulting from failure of vasoconstriction in the skin, and contributed by altered mentation.

Those at greatest risk are people spending extended time outdoors, including the homeless and outdoor recreationalists. The elderly and very young have a lower ability to centrally regulate body temperature. Children’s increased body surface area also leads to more rapid heat loss. People who are intoxicated with alcohol or drugs may not sense the cold or lack judgment to seek shelter. Alcohol also acts as a vasodilator, impairing vasoconstrictive adaptation to cold.

As the weather cools down, be mindful of how easily hypothermia can develop. Temperatures can be above freezing, yet those who are vulnerable are still at risk of hypothermia. Prepare yourself well for any snowy excursions, and keep an eye on those in your community who may not be able to seek shelter.

Stomach mucosa showing spots of black or dark brown discoloration
known as Wischnewsky spots. These are not specific to hypothermia and may just be an indicator of physiologic stress.
Bright pink discoloration over the knees, or “frost erythema”.
Pallor of the renal cortices corresponds to the microscopic “Armanni-Ebstein” lesion. This isn’t specific to hypothermia and can be seen in ketoacidosis from any cause.

-Alison Krywanczyk, MD, FASCP, is currently a Deputy Medical Examiner at the Cuyahoga County Medical Examiner’s Office.

Triaging Times

As a clinical instructor and lead cytologist at my institution, I like to remind our newer cytologists and cytology students of the importance of being prepared for FNA biopsies so they develop good habits or best practices as they become more experienced. This level of preparation helps to create a culture of ongoing learning and improvement, which is necessary for the laboratory. In my experience, I’ve met some cytologists who prefer to go into a case blind, with the mindset that knowing the patient’s clinical history in advance muddies their knowledge, skills, and abilities, limiting their mindset by excluding the possibility of other diagnoses. While diving into the unknown might seem exciting, it is also a hindrance and could result in errors, especially when the clinical history helps us triage the patient’s sample. For example, knowing that the patient has a history of lymphoma or that the presentation state includes bulky lymphadenopathy prompts us to collect additional needle passes to send for flow cytometry analysis. Another concern is not knowing whether the patient has a history of breast, gastric, or esophageal cancer, and consequently processing the specimen routinely, which may result in an extended cold ischemic time. This delay in fixation along with insufficient formalin fixation can yield false negatives on ER/PR IHC in breast cancers and HER2 FISH in breast, gastric, and esophageal cancers, which could restrict the use of hormone therapies, such as tamoxifen and aromatase inhibitors for hormone receptor-positive (HR+) cancers, or trastuzumab for HER2+ cancers. I cannot overemphasize the importance of familiarizing yourself with clinical history and communicating case specifics while you act as a mediator between clinician and pathologist.

Whether the clinical history impacts the pre-analytical phase, such as specimen collection (limiting cold ischemic time or collecting additional needle passes for ancillary studies) or the analytical phase, as such processing (formalin fixation) and diagnosis (selecting an appropriate immunoprofile), we must remain vigilant and proactive in laboratory medicine. In this case, knowing the patient’s clinical history was of the utmost significance as it helped to reduce the number of immunostains and ancillary studies necessary to make the diagnosis. Using morphologic criteria in tandem with the patient’s clinical history narrowed the differential diagnoses to just two possible types of cancer, presented below.

A 59 year old male patient presented to the emergency room after an automobile accident. On imaging, the X-ray and CT scan identified a left humerus mass and fracture, and bloodwork was performed. His medical record was sparse and uneventful with no recent visits or encounters. To build a more comprehensive wellness profile and prepare for surgery, he was also offered a one-time screening for Hepatitis C, as an adult who was born between 1945 and 1965.

The left humerus mass was biopsied via CT-scan guidance and two passes were obtained. The Diff-Quik stained smears demonstrate large polygonal cells, some with abundant, granular cytoplasm and some isolated cells with naked nuclei. Vessels also appear to traverse some of the cell groups.

Images 1-2: Bone, Humerus, Left, CT-guided FNA. Diff-Quik-stained smears.

The Pap-stained smears also demonstrate polygonal cells with granular cytoplasm, nuclei with coarse chromatin, and prominent nucleoli. An interesting feature frequently identified in this case is the intranuclear inclusions, and in hindsight, a focus on these may have further reduced the number of immunostains performed.

Images 3-5: Bone, Humerus, Left, CT-guided FNA. Pap-stained smears.

The H&E-stained cell block sections show trabeculae with endothelial wrapping around the cell cords. While renal cell carcinoma was listed as a differential diagnosis due to its telltale oncocytic cytoplasm and vascularity, hepatocellular carcinoma was favored.

Images 6-7: Bone, Humerus, Left, CT-guided FNA. H&E sections (6: 100x, 7: 400x).

Immunostains were performed using proper positive and negative controls on the cell block sections, and the tumor cells show positive staining for Arginase, cam5.2, and Hepar1, while negative staining for CK7 and PAX8 (not shown).

Images 8-10: Bone, Humerus, Left, CT-guided FNA. Cell block section immunohistochemistry. 8: Arginase-positive; 9: cam5.2-positive; 10: Hepar1-positive.

Fortunately, before ordering immunostains, both our cytologist and pathologist working on the case peered into the patient’s medical record and noticed that he had recent bloodwork which demonstrated a positive Hepatitis C screening. This diagnosis was as recent as the identification of his humerus mass. Had it not been for his car accident, I can’t imagine how long he would have gone undiagnosed for both hepatitis and metastatic hepatocellular carcinoma. Incidental findings save lives, folks.

Granted, in settings of unknown primaries with widespread metastatic disease, such as carcinomatosis, an extensive workup is almost always inevitable. Narrowing down possible etiology based on information such as gender, age, and environmental or occupational exposure can help, but that doesn’t always yield a definitive answer as time- or cost-effectively as possible. In this case, that one clue of untreated Hepatitis C was all the cytopathology team needed. A rarity, sure, but as we are asked to do more personalized tests with less material, think of the patient’s specimen as a puzzle and keep your eye out for a clue both under the microscope and behind the computer. You never know what you might find that reduces errors and unnecessary testing while efficiently leading to a definitive diagnosis.

-Taryn Waraksa-Deutsch, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

Microbiology Case Study: Severely Immunocompromised Female with Respiratory Failure

Case History

A 50 year old female with a complex medical history consisting of lymphoma, diabetes mellitus (type II), sarcoidosis, congestive heart failure, chronic renal failure (stage 3), and pancytopenia  presented to the emergency department with shortness of breath, cough, fever. She was found to be positive for SARS-CoV-2 and was transferred to the ICU due to hypoxic respiratory failure. She was treated for sepsis and respiratory failure, but her status continued to decline. The patient had multiple admissions due to COVID-19 in the past, received remdesivir and was on corticosteroid therapy due to the interstitial lung disease from last year. Initial evaluation included complete blood count which revealed anemia (hemoglobin=8.7 mg/dl), leukocytosis (WBC = 21,900/mcl), lymphopenia (910/mcl) and thrombocytopenia (Plt = 27000/mcl). The patient was treated with broad antibiotics and additional steroids. Additional tests revealed hyperproteinemia and hypoalbuminemia. Chest x-ray showed worsening infiltrates in lungs and chest CT scan revealed left apical hydropneumothorax, loculated left pleural effusion, pneumomediastinum, and chest wall subcutaneous emphysema. Lung biopsy revealed necrosis. Histopathology examination revealed broad, branching hyphae with sporulation in lung tissue biopsy and bronchoalveolar lavage. Respiratory cultures of lung biopsy and BAL grew rapidly and lactophenol cotton blue tape preps showed broad hyphae with round sporangium and rhizoids between the stolons. The patient was diagnosed with mucormycosis, infection with Rhizomucor, and was treated with Amphotericin B. Surgical debridement of the tissue was not possible due to her declining condition. She passed away after 5 days.

Figure 1. H&E stain of the lung biopsy (top, left) and Papanicolaou stain of bronchoalveolar lavage (top, right) revealed broad, ribbon-like, right-angle branching hyphae (visible in lung biopsy) with sporulation (credits to Dr. Elham Arbzadeh, George Washington University School of Medicine and Health Sciences). Rapid growth was observed from the respiratory cultures of the tissue biopsy by day 2 (bottom, left) where lactophenol cotton blue tape preps showed broad hyphae with sporangium (bottom, right) and intermodal rhizoids (not shown in this image).


The term mucormycoses refers to infections caused by the Zygomycetes which is further separated into Mucorales and Entomophthorales. Some of the members of Mucorales are Rhizopus spp., Mucor spp., Lichtheimia (Absidia) spp., Syncephalastrum spp., and Rhizomucor spp.1,2 These organisms live in soil, dung, and vegetative matter. Infection is usually acquired by inhalation/ingestion of their spores or direct inoculation and contamination of wounds. The mold can invade the walls of the blood vessels causing angioinvasion and often results in dissemination of mycotic thrombi and development of systemic infection. Zygomycetes are most commonly known for causing rhinocerebral, pulmonary, cutaneous, and disseminated disease. Infections with Zygomycetes most commonly occur as opportunistic infections in immunocompromised hosts. Risk factors include diabetes, those with acidosis, neutropenia, and sustained immunosuppression such as after transplantation.

Zygomycetes grow very fast (within 48 to 72 hrs.) and is often called a “lid lifter”. The colonies have a wooly mycelium and can be described as cotton candy-like. Lactophenol tape preps of the mold would reveal broad hyphae, aseptate or pauciseptate, ribbon-like hyphae with irregular width. At the tip of the sporangiophore, there is a sack-like structure called a sporangia with contains all the spores. Fungal elements and hyphae seen on tissue biopsies from patients with mucormycosis typically have near right angle branching (usually >40o) broad, non-septate hyphae. In contrary, those with aspergillosis show acute angle branching (usually <45o) with narrow, septate hyphae.3  

Genus-level identification can be achieved by microscopic morphology. Rhizomucor is an intermediate between Rhizopus and Mucor. Rhizoids found in Rhizomucor are few in number and are located on stolons, between the sporangiophores, as opposed to Rhizopus where the rhizoids are often seen directly at the nodes and Mucor which does not produce rhizoids. Sporangia (40-80 µm in diameter) are brown in color and round in shape. Apophysis is absent, which allows for differentiation from Lichtheimia (Absidia) where apophysis can be seen.4 The genus Rhizomucor includes three species: Rhizomucor pusillusRhizomucor miehei, and Rhizomucor tauricus.5

Treatment of mucormycosis consists of antifungal and surgical therapy. Amphotericin B is the most commonly used antifungal agent. Liposomal amphotericin B has also been successfully used in some cases with zygomycosis due to Rhizomucor.6  Early diagnosis and treatment are crucial and mortality rate is high.7  Of note, Zygomycetes are intrinsically resistant to voriconazole.


  1. Rippon J W. Medical mycology. The pathogenic fungi and the pathogenic actinomycetes. Philadelphia, Pa: Saunders; 1974. Mucormycosis; pp. 430–447. 
  2. Scholer H J, Müller E. Beziehungen zwischen biochemischer Leistung und Morphologie bei Pilzen aus der Familie der Mucoraceen. Pathol Microbiol. 1966;29:730–741.
  3. Mohindra S., Mohindra S., Gupta, R., Bakshi, J., Gupta, S. K. Rhinocerebral mucormycosis: the disease spectrum in 27 patients. Mycoses. doi: 10.1111/j.1439-0507.2007.01364.x.
  4. de Hoog, G. S., J. Guarro, J. Gene, and M. J. Figueras. 2000. Atlas of Clinical Fungi, 2nd ed, vol. 1. Centraalbureau voor Schimmelcultures, Utrecht, The Netherlands)
  5. Schipper M A A. On the genera Rhizomucor and Parasitella. Stud Mycol. 1978;17:53–71. 
  6. Bjorkholm, M., G. Runarsson, F. Celsing, M. Kalin, B. Petrini, and P. Engervall. 2001. Liposomal amphotericin B and surgery in the successful treatment of invasive pulmonary mucormycosis in a patient with acute T- lymphoblastic leukemia. Scand J Infec Dis. 33:316-319.
  7. Ribes, J. A., C. L. Vanover-Sams, and D. J. Baker. 2000. Zygomycetes in human disease. Clin Microbiol Rev. 13:236-301.

-Maryam Mehdipour Dalivand, MD is a Pathology Resident (PGY-1) at The George Washington University Hospital. She is pursuing AP/CP training.

-Rebecca Yee, PhD, D(ABMM), M(ASCP)CM is the Chief of Microbiology, Director of Clinical Microbiology and Molecular Microbiology Laboratory at the George Washington University Hospital. Her interests include bacteriology, antimicrobial resistance, and development of infectious disease diagnostics.

What’s NOT New in Cancer Care?

In June of 2017 just at the start of the annual American Society of Clinical Oncology (ASCO) meeting in Chicago, Illinois, there were at least 7 new FDA approvals for immuno-oncology agents targeting PD-L1 in cancer. At that time (2017), there were 2030 potential agents targeting 265 different targets across cancer including the modalities of t-cell targeted and other immunomodulators, cell therapy, cancer vaccines, oncolytic viruses, and CD3-targeted bispecific antibodies. Just three years later (2020), prior to the COVID-19 pandemic, this landscape had increased to 4720 potential agents targeting 504 targets across the same spectrum. That represents a 233% growth in these agents. Although only a fraction of these is “approved” (i.e., FDA approved and in use in patients clinically), many these agents are in clinical trials that require patient recruitment using pathology and other testing data. What does this mean for pathologists and laboratory professionals? Depending on the tumor being targeted and the target, there may or may not be a specific laboratory test that needs to be performed which may be routine, like histology parameters or immunohistochemistry, or may require advanced methods, like unique antibodies/clones, specific quantification methods, or molecular testing. The range of testing is not even unique to a specific therapy—for example, pembrolizumab uses staining for PD-L1, MSI, or no testing at all depending on tumor type. For the sub-specialized pathologist that focuses on one or two organs only, mastering the rapid pace and required diagnostic-therapeutic pairings is still a challenge. Imagine what it is like to be a general surgical pathologist in a community setting serving a community cancer center. Moreover, the diagnosis of a specific tumor is often completely disconnected for any biomarkers that may be indicated at the time of collection or several months later depending on therapeutic outcomes. This poses a range of problems in logistics and processing that are still being worked out at the individual system level. Still, the plethora of new treatments for cancer patients is very exciting.

In 2017, the largest group of targets (which was heterogenous) were tumor associated antigens (TAA) which are molecules that are not normally found in the human body produced by tumor cells as the result of changes to cellular processes. Whether it is hybrid proteins, glycosylation, or phosphorylation products, etc., these unique antigens held amazing promise as something we could target and destroy without fear of hurting normal human cells. However, the bulk of these approaches were for tumor vaccines (>90%) in 2017, dropping to 58% in 2020 (and from a total of 265 to only 198). To date, however, only a handful of cancer vaccines have been fully approved including sipuluecel-T for metastatic prostate and T-VEC for advance melanoma. This example category creates a complex set of challenges for pathologists and laboratory professionals. What data is needed about a patient or their tumor before a vaccine can be used? Does it require special studies that are not easily available or are costly? After vaccination, what follow-up tissue or blood studies are needed to follow the patient? Who dictates which tests are required before treatment: industry or medicine? But the more important challenge is: When do we, as the laboratory, pull the trigger to develop and disseminate such information and on-board new tests? Certainly, we are not going to look at Phase I trials and start taking about needs for future diagnostics. But by Phase III (where there is still a high dropout rate before full FDA approval) the number of potential agents and tests may still be daunting. If we wait until approval, now we are behind because our clinical colleagues will start immediately wanting to use the therapy. Tumor vaccines are an interesting category because we assume, for the most part, that there is likely only a diagnostic role needed. But then consider targets like CD-19, PD-L1, PD-1, CD3, Her2, CTLA-4, CD20, MUC1, CD22 and so on which are very familiar to our laboratory family because we often have already a test for these markers.

But is it the correct clone?

Do we have to score or interpret it differently?

When the agent is for cell therapy (the largest growth area of therapy development with 294% growth alone), what role does the transfusion medicine team play in administering or monitoring the patient?

As with the prior example, at what point do we, as a specialty of diagnosticians, dig into the forthcoming clinical trial results to plan? If our colleagues are in academic centers and are part of the clinical trials, they often are aware of and are administering the very tests that determine trial entrance. But if one reads just a few clinical trials of these agents, you may find that the inclusion criteria require a large battery of tests; however, on the other end when it is clinical ready for prime time, only one biomarker may be needed. Such a clustered landscape of information poses frustrating challenges for the clinical team and laboratory team in trying to find the way forward to get patients the life-saving therapies that are quickly arriving.

There is no question that the collision of targeted therapeutics and evolving diagnostics (i.e., precision cancer medicine) has demonstrated phenomenal growth with ever increasing benefits for patients. Affordability and access to these therapeutics aside*, studies continue to be completed and published including combinations therapies and hybrid therapies which show incredible promise. At ASCO 2022, the results of the DESTINY-Breast04 Phase III trial showed that trastuzumab deruxtecan (HER2-directed antibody and topoisomerase inhibitor conjugate) show a 49% reduction in the risk of disease progression or death versus physician’s choice of chemotherapy for patients with HER2-low metastatic breast cancer. That finding should be read a few times to make sure that the impact of this statement is very clear for pathologists and the laboratory. Previously, how we report HER2 (0, 1+, 2+, 3+) was complicated and often required FISH for questionable cases to look directly for HER2 amplification. This new category of patients requires reporting accurately 1+ or 2+ (FISH negative) disease, as it has incredible implications for patients. This news follows the recent new indications for CDK inhibitors in breast cancer related to Ki-67 mitotic score. Just when we thought breast cancer was straightforward, there is more to know and, more importantly, more time and tedium and standardization needed to report it for each patient. And, of course, early triple-negative breast cancer can also be treated with checkpoint inhibitors after PD-L1 testing is performed…but that’s literally old news as the data was release in 2020 at the start of the pandemic.

Outside of therapeutics, diagnostics are evolving quite rapidly with the COVID-19-induced ability to use digital pathology more readily creating a super-highway for artificial intelligence products to be validated for clinical use. PaigeAI has two such products (one for prostate and the second for breast lymph node evaluation released March of 2022) and many others are sure to follow. In parallel, screening, imaging, and surgery have also had advancements that continue to improve patient care and outcomes. So, it seems that everything feels new in cancer but is that the case?

The bulk of tumors diagnosed in the US (and elsewhere) are done with simply H&E staining (up to 75%) with another 20% being further confirmed by a few IHC tests (bringing the total up to 95%). This is not new and, most importantly, is the standard of care for the time being that we use to classify tumors. That classification has dictated, to some degree, the correct NCCN or other cancer protocol that oncologists used to treat patients. At some point, however, sufficient data on the bulk of all tumor types will likely point precision medicine treatments at all cancers. At that point, will a tissue biopsy be necessary with full histology or will a fine needle aspiration with molecular testing dictate the care? The credible assumption is that standard histology and IHC will remain in practice for the foreseeable future because so much billing, accreditation, and compliance is tied closely to them. But we CAN envision a “histology-free” oncopathology approach that matches patients to treatments with a panel of biomarkers. Sounds amazing but also stressful from the point of view of your typical anatomic pathologist.

*But the final thought on this, and perhaps the most important, is cost. Much like the domestic energy market is facing a dwindling pool of customers who agree to pay more and more for “traditional power” while their neighbors pump excessive kilowatts into the grid with their solar panels and windmills enjoying essentially “free power”, progress in cancer screening, detection, and treatment should be dwindling the pool of potential patients and increasing the costs to deliver care to the remainder. However, data and trends suggest that cancer is increasing globally. Why, if we are spending so much money and development on cancer care? Poverty and access. Cancer care is both expensive (in the US) and relatively expensive (in LMICs) with a focus on a small group of patients (0.55% of a population per year develop cancer). Projections of populations who need certain therapeutics are calculated using payer pools and markets that are existing and reliable. That does not include the bulk of LMICs. So, when we consider the cost of the PD-L1 checkpoint inhibitor class per year per patient is upwards of $125,000 USD, how can we even consider that an option for impoverished patients living off $1 USD per day? But if we don’t sort that out and treat these patients, we are assuming that persons who are impoverished are less valuable than persons who can afford expensive care. That evil logic, however, doesn’t hold true because even individuals in the US often become destitute or lose the bulk of their fiscal well-being when they must pay for cancer care—a situation that simply does not occur in countries with socialized medicine and/or universal healthcare.

Cancer care is rapidly evolving and the new tools and therapies available are incredible and miraculous for many patient types who would have faced a death sentence even 10 years ago. But with this amazing progress, we cannot ethically let people with limited resources succumb to these diseases over something so trivial as money. To do so poses harm and sets us up for failure as a species. It is for these reasons that ASCP engages in global health outreach. We are excited to have recently launched the Access To Oncology Medicines (ATOM) program with UICC and more than 2 dozen partners which will rapidly bring high-quality generic cancer therapeutics to low- and middle-income countries. In parallel with the St. Jude/WHO efforts on pediatric cancer globally, we will deliver quality cancer diagnosis and treatment to all patients everywhere.

If you want to learn more about PD-L1 testing and/or overcoming barriers to I-O in persons of color, new education from ASCP is available at no cost at

You can also check out our free educational resources on HER2-low breast cancer and Ki-67 testing in breast cancer at

Special thanks this month the Kellie Beumer (instructional design) and Melissa Kelly (monitoring and evaluation) from the ASCP medical education grants team for their thoughtful inputs into this piece.



-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.

Microbiology Case Study: How to “Pin” a Diagnosis

Case History

A 7 year old female presented to the emergency department with left sided abdominal pain and a temperature of 103 degrees Fahrenheit. Labs drawn showed mild leukocytosis with a CT scan suggestive of acute appendicitis. The patient underwent uncomplicated appendectomy with no complication. Gross examination of the appendix revealed an unremarkable, non-perforated serosa and a fecalith within the lumen. Representative tissue sections submitted for microscopic analysis per grossing policy. The findings below led to the submission of the entire appendix to be evaluated.

Figure 1. Low power image of an appendix demonstrating mild acute inflammation, lymphoid hyperplasia and congestion.

Figure 2. High power image, Cross-section of an adult female E. vermicularis from the same specimen shown in Figure 1. Adherent to the appendiceal surface. Note the presence of the alae (blue arrow), and the presence of almond shaped eggs (red arrow).


The nematode Enterobius vermicularis, widely known as the human pinworm, is one of the most common parasitic worm infections today in the United States, infecting approximately 40 million people. The patient population is often children who are infected via fecal-oral transmission, with autoinfection being common. Humans are the only known host of this nematode. Once E. vermicularis embryonated oocytes are ingested, the larvae hatch and inhabit the gastrointestinal system. At night, the larvae migrate down to the anus, lay their eggs, and the cycle recurs.

The clinical presentation can be asymptomatic or can present with perianal pruritus at night, which can be explained via the life cycle of the parasite as stated above. The method of choice for diagnosing E. Vermicularis is microscopic examination of the eggs via cellulose tape slide test. A piece of scotch tape collects the eggs near the perianal area of the patient, which is then used for analysis and identification of the eggs. Microscopically, E. Vermicularis can be identified by the spines or ‘alas’ on the surface with oval shaped, thick capsuled oocytes within, seen in figure 2. To improve the sensitivity of the scotch tape test, it is best to do this test in the early morning, when there is an increased chance of sampling the eggs.

Rarely, is this worm associated with any severe symptoms but patients can present with abdominal pain, suggesting intestinal obstruction, extra intestinal manifestations like vulvovaginitis, or appendicitis. The relationship between E. Vermicularis and appendicitis is up for debate as to whether there is a causative relationship or if it is an incidental finding seen within appendicitis. Regardless of the relationship, once a diagnosis of Enterobius vermicularis is made, treatment with an anthelmintic needs to be given to the patient, such as Albendazole or Pyrantel Pamoate. In addition, treatment for everyone in the household needs to be considered in confirmed cases of infection.

Routine surgical specimens, such as appendices, can perhaps be overlooked once acute inflammation is noted. It is important to be able to identify organisms, such as pinworms, on such specimens to get the patient the appropriate treatment.



-Alexandra Medeiros, MD, is a first year anatomic and clinical pathology resident at Medical College of Georgia at Augusta University. Her academic interests include Forensic pathology, and surgical pathology.

-Hasan Samra, MD, is the Director of Clinical Microbiology at Augusta University and an Assistant Professor at the Medical College of Georgia.

Microbiology Case Study: A 26 Year Old Female with Diarrhea

Case Description

A 26 year old female with a past medical history of Hemoglobin SC disease (Hb SC) and iron deficiency anemia presented to the emergency department with lower abdominal pain and diarrhea for three days. She began having multiple episodes of watery diarrhea, followed by bloody diarrhea after eating at a restaurant. During this time, she also had fever, chills, body aches, and headache. The patient had been on a course of ceftriaxone and metronidazole started three weeks prior for sore throat, ear infection, and bacterial vaginosis. She completed her metronidazole course prior to the current illness. Abdominal computed tomography revealed splenomegaly and a mildly dilated, fluid-filled appendix without evidence of infectious or inflammatory abnormalities. Hemoglobin on admission was 11.1 mg/dL (Reference Range: 11.2- 15.7 mg/dL) and MCV 62.9 fL (Reference Range: 79.4- 94.8 fL), which is similar to her baseline.

Laboratory Identification

The patient underwent work up for community-acquired diarrhea. Stool cultures grew non-typhoidal Salmonella (Image 1). Blood cultures performed at the time of admission flagged positive with gram negative rods which were also identified as Salmonella species by MALDI-TOF. The organism was susceptible to ampicillin, ceftriaxone, ciprofloxacin, and trimethoprim/sulfamethoxazole. The patient continued on intravenous ceftriaxone and responded to therapy. She was discharged home on oral ciprofloxacin.

Image 1. Salmonella Microbiologic Diagnosis using Xylose Lysine Deoxycholate agar and Triple Sugar Iron slant. A) Non-typhoidal strains of Salmonella are lactose non-fermenting, hydrogen sulfide producing (black colonies) enteric Gram-negative rods on Xylose Lysine Deoxycholate agar (XLD agar). B) Non-typhoidal strains of Salmonella are Alkaline (pink) over Acid (yellow) with the production of copious amounts of hydrogen sulfide on Triple Sugar Iron agar (TSI).


Hemoglobin SC disease (Hb SC) is the second most common hemoglobinopathy after Sickle Cell Disease (SCD, Hb SS) globally.1 Hb SC disease occurs when a patient inherits both hemoglobin S and hemoglobin C alleles. Hemoglobin S and C variants are caused by point mutations in the hemoglobin beta- chain, and both variants lead to reduced affinity to the alpha-chain. While hemoglobin C is an abnormal form of hemoglobin that does not cause sickling on its own, when co-inherited with hemoglobin S, the beta chains polymerize, causing red cell sickling when oxygen tension is lowered in the blood.2 Patients develop anemia due to reduced red cell lifespan (27-29 days for Hb SC vs. 15-17 days for Hb SS) and subsequent destruction of red blood cells.3

Complications arise from vascular occlusion and destruction of red blood cells, leading to gallstones, pulmonary infarction, priapism, and/or cerebral infarction. Other complications include avascular necrosis of the femoral head, bone marrow necrosis, renal papillary necrosis, retinopathies, splenomegaly, and recurrent pregnancy loss. Although Hb SC patients often exhibit similar symptomology to sickle cell disease, symptoms are typically milder and present later in childhood.2,3 In comparison to patients with Hb SS, Hb SC patients have milder anemia, less frequent sickle cells, and less severe hemolysis. While Hb SC patients have fewer sickling episodes compared to Hb SS patients, Hb SC patients have more severe retinopathy and splenomegaly. It is also important to note that the enlargement of the spleen is often caused by red blood cell sequestration and the optimal function of the spleen is significantly reduced (functional hyposplenia), which can lead to increased risk of infection from encapsulated bacteria.

Diagnosis of Hb SC disease is typically made by performing hemoglobin electrophoresis (Image 2). Hemoglobin electrophoresis separates the differing varieties of hemoglobin by size and electrical charge. Capillary electrophoresis separates hemoglobin variants based on the “zone” of detection where each variant hemoglobin appears based on a reference pattern. Normal hemoglobin (A, F, A2) is easily discriminated from variant hemoglobins (S, C, E, D), and quantification allows for detection of beta-thalassemia (increased A2 fraction). While useful as a screening tool, the hemoglobin variants identified in the “zones” are not specific. For example, Hb C and Hb Constant Spring share a zone, and Hb A2 shares a zone with Hb O- Arab. Variants detected by capillary electrophoresis are confirmed by a second method, and in this case Hb SC was confirmed by acid agarose gel (Sebia Hydrogel). When subjected to acid gel electrophoresis, Hb C and Hb S migrate in separate bands, while Hb A, A2, D, and E comigrate in the “A” band, and the “F” band may contain F in addition to the glycated fraction of normal adult Hb A. Patients with Hb SC disease will have variants detected in the S and C zones in capillary electrophoresis and lack signal in the A zone.4

Image 2. Laboratory Diagnosis of Hb SC disease includes hemoglobin electrophoresis and peripheral blood smear review. A) Hemoglobin capillary electrophoresis (pH 9.4) separates F, S, C, A2, A (Sebia, Capillarys 2 Flex Piercing). B) Acid agarose gel (pH 6.0-6.2) separates hemoglobins F, A, S, and C (Sebia, Hydragel Acid QC lane).  C) Peripheral blood smear morphology showing characteristic Hb SC forms including target cells, boat shaped cells (single arrow), red cell with crystals (double arrow), and hemighost cells (triple arrow).

Examination of the peripheral blood smear from a patient with Hb SC disease (Image 2C) reveals frequent target cells, boat-shaped cells (taco shaped), and only rarely contains classic sickle cells. Hemoglobin C crystals can be seen, both free floating and inside red cells, a feature of CC and SC disease but not seen in SS disease. Hemi-ghost cells and cells with irregular membrane contractions are also more frequent in Hb SC disease. In contrast, sickle cells are rarely observed in peripheral smears from Hb SC patients.

Salmonellaeare flagellated gram negative bacilli that are members of the Enterobacterales. Salmonellosis is typically foodborne in nature and presents as a self-limiting acute gastroenteritis.5,6 However, these organisms can invade beyond the gastrointestinal tract resulting in bacteremia.6 This case presents Salmonella as a cause of bacteremia in a patient with Hb SC disease following a bout of gastroenteritis. Although there is a well-known association between SCD and invasive infections with Salmonella, the incidence of Salmonella infection in patients with Hb SC disease has not been well studied. Patients with SCD, particularly those in Africa, are at risk for developing invasive disease caused by non-typhoidal Salmonella, including osteomyelitis, meningitis, and bacteremia. It has been hypothesized that disruptions in the gut microbiome and increased permeability of enterocytes makes SCD patients more prone to invasive Salmonella infections.6 Furthermore, the compromised function of the spleen in both patients with SCD and Hb SC disease increases the risk of disseminated infection by encapsulated bacteria and Gram negative rods. The spleen plays an important housekeeping role removing old or damaged erythrocytes, but also has an important immunological function housing memory B cells, producing antibodies and macrophages that phagocytize circulating bacteria, particulates or other debris and then present the antigens to other immunological cells in the spleen.7 Although sepsis caused by Salmonella is an occasional progression of gastroenteritis, this patient’s Hb SC disease likely increased the likelihood of bacteremia because of her functional asplenia.


  1. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331–6.
  2. Tim R. Randolph,24 – Hemoglobinopathies (structural defects in hemoglobin),Editor(s): Elaine M. Keohane, Catherine N. Otto, Jeanine M. Walenga,Rodak’s Hematology (Sixth Edition), Elsevier, 2020, Pages 394-423, ISBN 9780323530453,
  3. (
  4. Nathan, D. G., Orkin, S. H., & Oski, F. A. (2015). Sickle Cell Disease. In Nathan and Oski’s hematology and oncology of infancy and childhood (8th ed., pp. 675-714). Philadelphia, PA: Elsevier. Retrieved from!/content/book/!/content/book/3-s2.0-B9781455754144000206. Accessed 2022
  5. Bain, BJ. (2020) Haemoglobinopathy Diagnosis, Third Edition. Hoboken: John Wiley and Sons, Ltd
  6. Kurtz, J. R., Goggins, J. A., & McLachlan, J. B. (2017). Salmonella infection: Interplay between the bacteria and host immune system. Immunology letters190, 42–50.
  7. Lim, S.H., Methé, B.A., Knoll, B.M. et al. Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?. J Transl Med 16, 239 (2018).
  8. Leone G, Pizzigallo E. Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases. Mediterr J Hematol

-John Stack is a first year AP/CP resident at UT Southwestern Medical Center.

-Marisa Juntilla is an Assistant Professor in the Department of Pathology at UT Southwestern Medical Center. Dr. Juntilla is a board certified Clinical Pathologist and is certified in the subspecialty of Hematopathology.

-Dominick Cavuoti is a Professor in the Department of Pathology at UT Southwestern Medical Center. Dr. Cavuoti is a board certified AP/CP who is a practicing Clinical Microbiologist, Infectious Disease pathologist and Cytopathologist.

-Andrew Clark, PhD, D(ABMM) is an Assistant Professor at UT Southwestern Medical Center in the Department of Pathology, and Associate Director of the Clements University Hospital microbiology laboratory. He completed a CPEP-accredited postdoctoral fellowship in Medical and Public Health Microbiology at National Institutes of Health, and is interested in antimicrobial susceptibility and anaerobe pathophysiology.

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

BOGO: Biopsy One, Get One Free

I’ve mentioned before how important it is to know clinical history before attending a biopsy, and I cannot stress this point enough. As the first line of screening, the intermediary between clinician and pathologist, the role of the cytologist is to prepare, assess, and convey. In a cancer center, we have three main populations: the patients with the unknown primary, the patients with the suspected primary, and the patients with the suspected metastasis. In the event of a suspected metastasis, we’ll review previous relevant pathology material if we have it onsite. Unless the clinician is requesting additional prognostic markers, the review process helps us eliminate the unnecessary repetition of immunostains (IHC) by confirming that the current material is morphologically consistent with the prior material. Sometimes we still perform old-school cytology without a plethora of ancillary studies. HA!

Most of the endobronchial ultrasound (EBUS) procedures performed at our institution are for lung cancer staging or differentiation between a lung cancer metastasis and an extra-pulmonary metastasis. Not that we don’t see the occasional sarcoid- or anthracosis-related process from time to time, but our most common indication is cancer. For an 88-year-old male patient with multiple lung nodules and both mediastinal and hilar lymphadenopathy, confirmation of metastasis was the main objective of the EBUS procedure. The patient’s pertinent medical history includes former tobacco use, squamous cell carcinoma of the lung (diagnosed percutaneously in 2022), clear cell renal cell carcinoma (s/p partial nephrectomy in 2020), prostate cancer (radiated in 2007), melanoma (excised in 2001), and cutaneous squamous cell and basal cell carcinoma (also previously excised in 2002 and 2008). With an extensive cancer history, the lung nodules and thoracic nodes could be any of them, although metastatic squamous cell carcinoma of the lung was clinically favored. My awesome cytologist colleague, Kelly, attended the EBUS procedure. The Rapid Onsite Evaluation (ROSE) was a clear-cut “adequate for diagnostic material,” and the attending pathologist added “tumor cells present.” The following morning, Kelly stopped by my desk to ask my opinion of the 12R (right hilar) lymph node she was screening. She said, “look at my dots. Do these look like the same cells to you? Or are they different? Because I feel like they’re different.” Before putting the slide on my scope, I asked, “so… like a combined adenosquamous? Or a small cell component?” She replied, “not small cell. Something… I don’t know, but they look different. The patient was recently diagnosed with lung cancer and has a history of renal cell.” I fixated on the H&E cell block slides (Images 1-3) before perusing the Diff-Quik and Papanicolaou-stained slides (Images 4-5). “Uhm… Why are there two different types of tumor cells here?! The cytoplasm here is so… vacuolated, but it’s not quite like lung adeno, and the other group… even the n/c (nuclear-to-cytoplasmic) ratio is different. What is this?” Kelly replied, “okay, so there are definitely two different types of tumor here.” I looked up, “It has to be. Absolutely, yes.”

Images 1-4. Lymph node, 12R, EBUS-guided FNA. 1-3: H&E cell block sections 1, 100x; 2, 400x; 3, 100x. 4: Diff-Quik stained smear.
Image 5. Lymph Node, 12R, EBUS-guided FNA. Pap-stained smear.

Kelly entered her diagnosis into our laboratory information system and brought the case over to the pathologist on cytology service for the day. She explained her thought process, and the pathologist also questioned if it was a combined process, such as a lung adenosquamous and maybe the original lung biopsy only sampled the squamous component. With the most recent clinical history of both lung squamous cell carcinoma and clear cell renal cell carcinoma, an IHC panel was appropriately selected. Later that afternoon, the pathologist exclaimed, “IT’S BOTH! IT’S SQUAMOUS AND RCC!” The clusters of squamous cell carcinoma did not stain for PAX8 (a renal cell carcinoma marker) (Image 6), and the same cluster stained positive for p40 (a squamous cell carcinoma marker) (Image 7). Within the same level of the cell block, the cluster of cells that appeared morphologically different than squamous cluster stained positive for PAX8 (Image 8) and negative for p40 (Image 9), confirming a renal cell carcinoma component. A small focus of p40-positive cells was present next to the p40-negative renal cell carcinoma (Image 9), further demonstrating mixed histology. This finding was shared with other pathologists, and the results were immediately called to the pulmonologist as this was a critical finding. Sometimes we encounter a partially involved node where the tumor cells are intermixed with lymphocytes, sometimes the lymph node yields more tumor than the primary site, and sometimes, albeit rarely, we encounter a lymph node infiltrated by two different carcinomas.

Images 6-9. Lymph Node, 12R, EBUS-guided FNA. Cell block section immunocytochemistry. Squamous cell carcinoma cluster – 6: PAX8-negative; 7: p40-positive. Renal cell carcinoma cluster – 8: PAX8-positive, 9: p40-negative (with small focus of p40-positive squamous cell carcinoma).

Due to the patient’s bulky disease and PD-L1 expression of 30%, the medical oncologists primary aim was to treat the squamous cell carcinoma first and follow up renal cell carcinoma therapy second. After the first few cycles of treatment, the lung nodules have decreased in size, but the thoracic nodes remain unchanged. Once the squamous cell carcinoma is controlled or demonstrates a more significant response, immunotherapy may be added to target both, with a tyrosine kinase inhibitor directed at renal cell carcinoma metastases in the event of progression.

-Taryn Waraksa-Deutsch, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

“Being a Doctor” Vs. “Doing Your Job”

I awoke to a text recently that simply said, “Can I ask you a question?” Having finished medical school 22 years ago, I get this very frequently and know from personal anecdotal statistics that it’s either a medical issue (high probability) or someone needs money (much less common). This is not a text from work nor is it from a channel that will result in additional funds deposited on my behalf. This is from an acquaintance, by which I mean it could be any of the following: family member, friend, colleague, ex-girlfriend of an ex-boyfriend, co-worker, random person I met somewhere, etc. I spent some time on the phone in response to this text, recommended a course of action, and solved the problem. The details of this discussion (or the hundreds of others I had over the years) are privileged and irrelevant. The point is that I was “being a doctor’. A problem was presented by a person in need with real concerns about their health (or a loved one’s), I assessed the information they provided, and suggested a next step. My advice is usually spot on and appreciated which stems from my being cautious but concerned. Another important feature of my advice derives from one of my mantras: “Don’t scare the straights!” (which I learned from the comic genius, Bill Murray, in Ghostbusters).

This is one of the hardest aspects of being a doctor (especially when you are a student). It’s really great that you recognize (sometimes immediately) that someone has a life-threatening illness… but they don’t need to know that unless they are within a safe, secure medical environment where action can be taken. Moreover, medical issues are private for the same reason. It’s pretty clear to all of us that we shouldn’t yell “Fire!” in a crowded theatre or even jokingly say words that sound like “bomb,” at an airport. But here’s a true story of what I mean with medicine. Many years ago, I happen to be on an airplane (at cruising altitude) coming back from Africa, where my friend, Paul Farmer (RIP), was also a passenger. Another colleague of ours (a surgeon) was also on the plane. Paul was having an eye issue which looked mild but irritating. Our colleague said, loudly in her confident tone, “Do you think it could he Ebola?” Paul and I exchanged a quick glance, both thinking, “Don’t scare the straights!” I think you see my point. But, for clarity, a personal example. One winter, my husband and I were returning from the city to our suburb, which required a brisk, long walk from the train. The sidewalks were icy and, in places, uneven. He stepped off and fell full force on his shoulder. The next morning he couldn’t move it and it was painful. My immediate thought was, “He broke his shoulder.” Did I say, “Dude, you totally broke your shoulder!” No. We were having an open house to sell our place and he was all stressed about it. So, I said, “Be careful with your arm and we will go to urgent care afterward.” This made him calm. I even made him drive to urgent care (it was not his dominant shoulder) to reassure him he was okay. In urgent care, the ortho surgeon (who happened to be that day’s coverage) walked in after the x-ray and said, “Dude, you broke your shoulder!” And my husband promptly passed completely out onto the examination table. It’s all about understanding the acuity of the situation and striving to not make it worse.

Have I ever been wrong? Of course! Because the only way to truly care for a medical concern is to evaluate it yourself in person with appropriate tools. And almost all of the times I have been wrong (which is only a few), there was some crucial aspect that was not shared because either it wasn’t known or there was discomfort with sharing.

But what I am describing is not unique to me. I’m quite sure every doctor gets these calls with frequency. It’s the purest form of practice because there is no financial transaction presumed, assumed, or demanded.

But what about “doing my job?” Let’s break that down. I work for a non-profit and have a private consultation practice (non-overlapping, non-conflicting). Currently, I am financially compensated (at about $175/hour (pre-tax)) for any/all of the following: health system implementation, grant writing/administration, education, research management, social media production/communication, expert scientific/business consultations, committee participation, abnormal laboratory case review, daily laboratory management, intra-operative consultation, market insights/research, etc. Not much of that sounds like I’m fighting death and stamping out disease at the individual patient level, the life task I as trained for in medical school. Importantly, I’m also hard salaried across all my work so I don’t do individual billing except for a few things like abnormal slide review. Many of my physician colleagues do have to engage in individual billing. But I think much of what I do still sounds very familiar to many of my physician colleagues who see patients every day. When (in my opinion) my physician colleagues should be spending every hour of every day “being a doctor,” as I described above, I fear they spend a lot of time instead documenting, managing, and administrating to ensure they are compensated. I am of the very unpopular opinion that healthcare should be free but I also believe healthcare workers should be compensated aligned to their impact on patients. The medical profit insistence paradigm continues to widen inequity while decreasing the care time for patients in lieu of format/template/documentation to justify billing. I have to spend time doing this non-patient care but, fortunately, they are limited because of the narrow slice of medical billing to which my services are privy.

Here is a specific example to demonstrate the difference I’m discussing. I received an abnormal smear to review from the laboratory. The white blood cell count was over 400,000 cells (ref 10 – 30), the smear was a “medical student”-level diagnosis, the patient was on a supposedly effective treatment, but they had left against medical advice. There are many ways to respond to this case. My question was, “Is this patient okay, right now?” and my immediate action reflex said, “This patient needs to see an oncologist right now.” But she left AMA. How you as a patient or doctor respond to this says a lot about you as a person but also about the fiscal constraints in which you work. What did I do? I called the patient who had, thankfully, been admitted elsewhere, and asked them to please have their doctor call me back. The doctor did, I told them the information, and my suggestion that oncology see them immediately. Oncology saw them a few hours later. Let’s summarize. I spent about 20 minutes reviewing all of the clinical and laboratory information, about 1 hour on the phone over 2 days, and about 10 minutes documenting all of this in the patient’s medical record. I was subsequently paid an additional $25 two months later for that documentation by the patient’s insurance company. So, I “did my job” for $16.67/hour over my base but I was also “being a doctor,” which likely was best for the patient. Which is most important at the end of the day? I certainly didn’t need the extra $25 but the patient definitely needed my input. Importantly, note that the insurance company valued my time at a 10-fold lower rate than did my hospital.

A recent study demonstrated that when nurse practitioners are used instead of physicians, healthcare costs were higher.1 This study follows other studies which have shown the opposite. I don’t have an opinion about quality of care, appropriateness, or territorial pissings in the current debate between MDs and NPs about scope of practice; in fact, I see NP’s quite frequently for my healthcare. But we are all being asked to always be conscious of costs in healthcare when all we should be focusing on is, “How is the patient doing right now?” Grand efforts, like task shifting domestically and internationally, are assumed to save money but they simply don’t do so universally. Where costs could be easily cut (i.e., administration) or outsourced (i.e., finance, HR, IT), they aren’t because C-suites are in charge of cost cutting. But doctors (and NPs and all front line medical workers) are the ones being told to be cost conscious and find cost savings—when their job should only be asking the question, “How is the patient doing right now?”

I love “being a doctor,” especially when I can help someone reach a positive outcome. I love “doing my job” because it’s variable, ever-changing, challenging, rewarding, and I feel my compensation is appropriate. I really love when “doing my job” and “being a doctor” align around the same task. Finding this alignment as frequently as possible produces the happiest healthcare workers and the best care for patients, in my opinion.

Note: As an employee of a 501(c)(3), my salary information is public knowledge.



-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.