This last month, I rotated through our Children’s hospital, which included reviewing hemoglobin electrophoresis tests. I’d learned about them before in residency, but they can be quite more interesting (complicated) than I expected.
Hemoglobin electrophoresis is a blood test to look at different types of hemoglobin to determine if there are any abnormalities. In a children’s hospital it is frequently ordered as a reflex for an abnormal newborn screen or when a child is incidentally found to be anemic. The test is performed in 2 stages. 1st lysed blood samples are run on gel electrophoresis and different types of hemoglobin are separated as they move at different speeds. Several types of hemoglobin will run within the same region, so a secondary method of separation is always employed.
Below, you can see how some bands in the same area of an acidic gel (agarose) are actually very different on the alkaline gel (cellulose acetate) and vice versa.
At our hospital, we use HPLC and measure retention times of the hemolysate to quantify and identify different hemoglobin types present. As a basic primer you should recall that hemoglobin is a tetramer with a pair of alpha globin + a pair of either beta, delta or gamma globin (each separate genes).
Alternative hemoglobins are enriched in populations where malaria is endemic as these variants may provide improved fitness by promoting resistance to the malarial parasite that reproduces inside red blood cells. Thus, many people of African or south east Asian descent may carry these variants.
Our case is that of a 2 year old girl with anemia who had testing sent by her primary care doctor for the following CBC:
This is indicative of microcytic anemia, but unlike some Thalessemias the RBC isn’t very high. More on this later.
Looking at the gel result, there is a large band in the area coinciding with Hgb C. We also see the normal Hgb A2 and a small amount of Hgb F. We know Hgb F can be increased in Hgb SS and thus could also be present if she had Hgb C trait or disease.
Looking at the next HPLC result, we see there is a similar very high level of Hgb C (68%) with corresponding levels of Hgb F and Hgb A2 (note: acetylated Hgb F and Hgb F are added together). Thus, this fits with a homozygous C with some compensatory A1 and F, right?
Remember Hgb C is a β -globin variant and you only have 2 β -globin genes, so if you are homozygous for the C variant on the β-globin gene (HBB), then Hgb A1, which is made of normal β-globin would be impossible to produce. Also you might be bothered by all of these small peaks. However, there are often small peaks that can’t be definitively identified and are likely post-translationally modified hemoglobin. But in the context of an abnormal Hgb A1 that shouldn’t be there, we dug deeper.
One of the most common hemoglobinopathies is Beta Thalassemia (β-Thal), which clinically manifests when less of the beta hemoglobin protein is produced. Heterozygous mutations lead to Beta Thalassemia minor with minimal symptoms, while homozygous mutations lead to β-thal major with symptoms of anemia. Mutations in the β -globin gene, HBB, can lead to complete loss of β-globin (β0 variant) or partial of β-globin (β+ variant).
As this patient has less than 50% of Hgb A present (expected amount), they could also have a β+ variant as well. This would make them compound heterozygous for C and β+.
One of the hallmarks of Thalassemia is an increase in Hgb A2 (normal 2.5-3.5%). Hemoglobin A2 is a normal variant of A that is composed of two alpha and two delta chains (δ2α2). We see in our case that the Hgb A2 is normal at 2.5%. So it seems the patient doesn’t display a typical Thalassemia picture.
One condition that could create this scenario is if there is a variant in the delta chain of A2 that causes it to elute differently. Indeed, there is a delta variant that creates hemoglobin A2 prime (A2’) that moves near the S region of the HPLC. And when we look back at our unknown hemoglobins, Hgb X is marked at 1.03 of the S region and has an abundance of 3.9%. This supports it being the Hgb A2’ and if we add this together with the Hgb A2 we get an elevated 6.6% A2 total, which would be consistent with Beta Thalassemia. Lastly, one would wonder if we could find this third hemoglobin variant A2’ on the alkaline gel. Previous studies have shown the A2’ variant is more negatively charged, so on a basic gel, it should move further from the negative anode than the other hemoglobins. We don’t see anything to the left of the HgbC, but if we flip the gel over and look under the patient label, you can see a faint band that is likely the A2’!
In summary this case arose from 3 separate mutations in a single patient. She was compound heterozygous for a Hgb C and β+ variants in the β-globin gene and she was heterozygous for an A2’ variant on the delta-globin gene. This was certainly a case where paying close attention mattered.
- Abdel-Gadir D, Phelan L, and Bain BJ. Haemoglobin A2′ and its significance in beta thalassaemia diagnosis. Int J Lab Hematol. 2009 Jun;31(3):315-9. doi: 10.1111/j.1751-553X.2008.01038.x. Epub 2008 Feb 21.
-Dr. Charles Timmons MD PhD is a pediatric pathologist at Children’s Medical Center in Dallas, TX. His responsibilities include signing out hemoglobin electrophoresis, HPLC and globin sequencing, and has been residency director for 17 years.
-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 interpretation.
The patient is a 72 year old
woman who presented to her physician’s office with postprandial pain and
unintentional weight loss. A CT scan was performed that showed no obvious
abnormality or cause for the patient’s abdominal pain. The patient subsequently
underwent an EGD and EUS which revealed enlarged gastric folds
without hemorrhage. In addition, there was wall
thickening seen in the body of the stomach within the luminal interface, superficial mucosa, deep mucosa
and submucosa consistent with possible
gastritis versus an infiltrative process. The remainder of the EGD and EUS was
grossly unremarkable. These findings
were concerning for possible linitis plastica. Pathology on the samples taken from the EGD were consistent
with poorly differentiated adenocarcinoma
that was invasive in both the gastric fundus and gastric body. The patient was initially taken to the operating room for
a staging laparoscopy to ensure that there was no metastatic disease before
beginning a preoperative chemotherapy regimen. The staging laparoscopy revealed
a thickened gastric wall from the fundus to the antrum, consistent with linitis
plastica, and no obvious evidence of metastatic disease. The patient then
underwent peritoneal washings which showed no evidence of positive cytology. Based
on these findings, the patient was started on a chemotherapy regimen of
epirubicin, cisplatin and fluorouracil (5-FU), which she tolerated well. The
patient was then taken to the operating room for a total gastrectomy procedure
with Roux-en-Y esophagojejunostomy.
Received fresh for intraoperative consultation is a total gastrectomy specimen with a black stitch designating the proximal side. It was requested by the surgical team to have the proximal esophageal margin frozen to ensure that esophageal tissue was indeed present, as well as to exclude the presence of any carcinoma. The proximal margin was negative for carcinoma with squamous mucosa present. The stomach measures 17.0 cm in length with an internal circumference ranging from 14.7 cm proximally to 9.0 cm distally. There is a 1.0 cm long portion of attached duodenum with an internal circumference of 5.8 cm. The serosal surface of the stomach is glistening, pink-tan and smooth with a scant amount of attached yellow, lobulated adipose tissue and omentum along the length of one entire edge measuring 26.0 x 13.0 x 1.0 cm. The stomach is opened to reveal glistening, tan mucosa with irregular rugal folds which are diffusely nodular, predominantly in the body of the stomach. There is a 6.5 x 5.0 cm are of flattened mucosa in the pyloric region (Image 1). The wall thickness measures 0.5 cm throughout. There are no grossly identifiable masses or nodules. Gross images are taken and the serosal surface is inked entirely in black. The adipose tissue is examined for candidate lymph nodes. Representative sections are submitted as follows:
B1 FS: Frozen section remnants
B2-B6: multiple representative sections from the cardia
B7-B10: multiple representative sections from the body
B11-B12: multiple representative sections from the pylorus
B13: representative perpendicular section through the distal resection margin
B14: seven putative lymph nodes
B15: five putative lymph nodes
B16: three putative lymph nodes
B17: seven putative lymph nodes
B18: six putative lymph nodes
B19: three putative lymph nodes
B20: six putative lymph nodes
Histologically, the specimen consisted of diffuse, poorly differentiated, discohesive cells throughout all the layers of the stomach, penetrating into the serosa, with fibrosis, inflammation and signet ring cells present. In addition, angiolymphatic invasion was present. Based on the gross presentation and histologic appearance, the specimen was signed out as a diffuse gastric adenocarcinoma with a stage of T3.
As of 2018, gastric cancer is the sixth most common cancer with approximately 1.03 million cases, and the third leading cause of cancer deaths worldwide, resulting in 783,000 deaths. Due to a better understanding of epidemiology, pathology, and molecular testing, as well as advances in new forms of treatments, the incidence and mortality in gastric cancer has been declining over the years. Of the gastric cancer types, rates of intestinal type carcinoma have been decreasing, however, the incidence of poorly cohesive gastric carcinoma (PCGC) and signet ring cell carcinoma (SRC) has increased. In order to accurately discuss PCGC, there must first be a discussion about the standardization of gastric cancer subtype definitions. Poorly cohesive, signet ring cell, and diffuse gastric carcinomas have commonly been used interchangeably. In 2010, the World Health Organization defined poorly cohesive gastric carcinoma as being composed of isolated or small groups of tumor cells. If there was a predominance of signet ring cells, then it would be termed a signet ring cell carcinoma. Mariette et al. proposed that a PCGC composed of 90% or more signet ring cells should be classified as SRC. The term “diffuse” corresponds to the same term “poorly cohesive”, and because of this, I will be using the term “poorly cohesive” solely going forward. In addition to this, the term “linitis plastica” would commonly be used interchangeably, but is best used as a term to describe the macroscopic appearance of PCGC or SRC.
Gastric carcinoma is classified as either early or advanced stage to help determine the appropriate type of intervention. Early gastric carcinoma is defined as invasive carcinoma confined to the mucosa and/or submucosa, regardless of lymph node metastases or tumor size. These tumors are generally smaller, measuring less than 5 cm in size, and found most commonly on the lesser curvature of the stomach at the angularis. Histologically, early gastric carcinoma will commonly present as well differentiated, mostly with tubular and papillary architecture. If the biopsies are composed of only mucosa, then distinguishing between well-differentiated carcinoma and carcinoma in situ or high grade dysplasia can be difficult. The presence of stromal desmoplasia in invasive carcinoma can help differentiate it from intramucosal invasion, which can contain single tumor cells within the lamina propria. This is an important distinction to make as intramucosal carcinoma does metastasize. Advanced gastric carcinomas will present grossly as either exophytic, ulcerated, or infiltrative tumors. Histologically, advanced gastric carcinomas will invade the muscularis propria and demonstrate cytologic and architectural heterogeneity, with a combination of patterns.
The 2010 World Health Organization classification determined four major histologic patterns of gastric cancer, which will often present with a combination of elements from the other patterns:
- Tubular: Most common pattern in early gastric carcinoma, with branching, distended or fused tubules containing intraluminal mucus, and nuclear and inflammatory debris
- Papillary: Most common in the proximal stomach with epithelial projections containing an underlying fibrovascular core. Also, it is frequently associated with liver metastases and an increased risk of lymph node involvement.
- Mucinous: Extracellular mucin makes up at least 50% of the tumor volume
- Poorly cohesive (including SRC): Mixture of signet ring and non-signet ring cells. Signet ring cells will have mucin pushing the nucleus to the periphery of the cell.
Helicobacter pylori (H. pylori) is a gram negative infectious bacteria that has been linked to gastric cancer. H. pylori is present in about half of the world’s population and other than gastric cancer, it is also associated with chronic gastritis, peptic ulcer disease, and gastric lymphomas. The bacteria is typically acquired during infancy and will remain for life if left untreated, with reactive oxygen species being generated that are capable of causing DNA damage due to the chronic infection. In addition, H. pylori can induce hypermethylation, resulting in the inactivation of tumor suppressor genes. Although H. pylori infection is considered a strong risk factor for developing gastric cancer, more commonly in intestinal type than diffuse type gastric cancer, only a small portion of those infected with the bacteria actually develop the malignancy. It is believed that approximately 80% of distal gastric cancers are due to a H. pylori infection, whereas there is little association between H. pylori and cardia gastric cancers.
In PCGC, such as this case, it is generally diagnosed in younger patients without a gender bias. Although PCGC can be associated with an H. pylori infection, it is more commonly related to a mutation in the tumor suppressor gene epithelial cadherin, also known as E-cadherin and CDH1. PCGC presents as an infiltrative growth of poorly differentiated, discohesive malignant cells that appear to arise from the middle layer of the mucosa. These cells can infiltrate as individual cells or as small clusters, but usually do not form glands (Image 2). If the gastric wall becomes extensively infiltrated by malignancy, the wall can be thickened and rigid, a macroscopic presentation termed as linitis plastica, which can lead to pyloric obstruction. Within PCGC, numerous signet ring cells can be present, leading to SRC. There is also a hereditary form of poorly cohesive gastric cancer referred to as hereditary diffuse gastric carcinoma, with an autosomal dominant pattern of inheritance. Histologically, it will include hyperchromatic nuclei, occasional mitoses, patchy intramucosal signet ring cells in the lamina propria, and carcinoma in situ associated with pagetoid spread of tumor cells along the preserved basement membrane. Hereditary diffuse gastric carcinoma will present with multifocal tumors under an intact mucosal surface, making diagnosis difficult. In patients with a CDH1 mutation and a family history of gastric carcinoma, a prophylactic gastrectomy is often the recommended treatment option.
- Adachi Y, Yasuda K, Inomata M, et al. Pathology and prognosis of gastric carcinoma well versus poorly differentiated type. Cancer. 2000;89(7)1218-24.
- Cancer. World Health Organization. Who.int. https://www.who.int/news-room/fact-sheets/detail/cancer. Published September 20, 2018. Accessed September 18, 2019.
- Carcas LP. Gastric cancer review. J Carcinog. 2014;13:14. Published 2014 Dec 19. doi:10.4103/1477-3163.146506
- Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012;3(3):251–261. doi:10.3978/j.issn.2078-6891.2012.021
- Mariette C, Carneiro F, Grabsch HI, et al. Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma. Gastric Cancer. 2019;22(1):1-9 https://doi.org/10.1007/s10120-018-0868-0-
- Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol. 2015;21(40):11428–11438. doi:10.3748/wjg.v21.i40.11428
- Van Cutsem E, Sagaert X, Topal B, et al. Gastric Cancer. Lancet. 2016;388(10060):2654-64. https://doi.org/10.1016/S0140-6736(16)30354-3
- Weisenberg E. Diffuse (poorly cohesive) type carcinoma. Pathology Outlines. http://www.pathologyoutlines.com/topic/stomachdiffuse.html. Revised August 22, 2019. Accessed September 18, 2019
-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.
So far we have reviewed the different federal regulatory agencies responsible for establishing laboratory testing guidelines, a brief overview of the different roles each department plays, as well as a discussion on testing complexity. In today’s post we’ll cover the optional accreditations available to labs, and how accreditation differs from certification.
In the simplest of terms, certification is a mandatory requirement, whereas accreditation is optional. Certification is required in order for laboratories to receive payments from Medicare or Medicaid. Laboratories must meet the minimum requirements set forth by CLIA to earn and maintain their certification status.
Accreditation is an extra additional step that laboratories can take to set themselves apart from neighboring labs by holding themselves to a higher standard. Accredited laboratories must still adhere to the minimum CLIA requirements, but there are additional rules and requirements to be satisfied depending upon the different accreditation agencies.
More rules and paperwork, why would anyone volunteer to take that on? Depending on the size, complexity, and client population that your lab serves, the benefits to obtaining accreditation can greatly outweigh the challenges of maintaining that accreditation status.
One of the requirements to maintaining your CLIA certification is routine inspections to confirm compliance with the rules. Accreditation agencies require inspections as well, but thankfully in most cases your CLIA inspection can be satisfied by your accrediting agency; meaning your lab will receive a single inspection to satisfy both groups. Results will vary for each lab, but generally speaking the accreditation inspections are perceived to be easier to get through than those conducted by the federal inspectors. For example, agencies like The CAP and COLA tend to be more focused on sharing of ideas and good laboratory practices, rather than coming in as the “lab police” and looking only for problems. The explanation of their regulatory requirements tends to be more user friendly and easier to interpret as well, rather than the formal CLIA laws which are legal documents and read as such.
Recognition by an accrediting agency confirms that the laboratory is qualified and competent to perform testing for which it has received the accreditation for. This stamp of approval can help patients and clients feel comfortable in choosing your laboratory for their testing needs. For laboratories that perform testing as part of clinical trial evaluations, this can help reduce the number of requested on-site audits by the client themselves, as the client may choose to rely on the third-party accreditation assessment due to their high standards. It may also help encourage new clients to choose you for their testing needs, as the accreditation confirms your commitment to higher quality standards.
Another possible benefit of having accreditation status is the impact on your laboratory staff. Continually striving to raise the bar on your standards and going above the bare minimum instills a sense of professionalism in your employees. By continually reviewing the regulations and preparing for or responding to inspections, staff are more likely to be committed to complying with your organization’s quality management system and standards of performance. Staff who are familiar with the requirements and the reasoning behind why a certain task is performed or documented, are more likely to comply with those policies and procedures.
There are currently 7 CLIA approved accreditation agencies: https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/Downloads/AOList.pdf. Some agencies are focused on a specific discipline, such as AABB for transfusion medicine, and others are more encompassing for all of the laboratory departments. Organizations looking to become accredited should research each option in order to determine which ones would be best to meet their specific needs. It is also common for labs to maintain more than one accreditation at a time, for example AABB and CAP. As always, the regulatory agency with the most stringent rules would be the ones the lab is expected to adhere to. In cases of joint accreditation, multiple inspectors may be needed to complete the biennial inspection; however the agencies will try to coordinate efforts and work together so that the inspections occur simultaneously. Sticking with our AABB & CAP example, CAP will work with AABB to locate an AABB approved inspector for the transfusion medicine checklist, while the remainder of the CAP inspection will be carried out by CAP inspectors. The AABB inspector would then inspect the transfusion medicine department for compliance with both CAP and AABB requirements at the same time.
The accreditation process may be challenging, but once you have obtained that esteemed status, the opportunities for continual education and improvement of your laboratory will be endless.
-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.
The patient is a 61 year old male in good health until about 4 weeks prior to presentation when he sustained a tick bite on his left arm. He subsequently developed chills, fatigue, loss of appetite, and weight loss. Concerned that his symptoms were not improving, the patient presented to urgent care and a CBC was ordered. His CBC was remarkable for mild anemia (RBC count 3.96, HB 12.9) and thrombocytopenia (platelet count 78,000/cmm). Review of the peripheral blood smear revealed organisms present within his neutrophils. Given his history of a tick bite, Doxycycline was initiated for 14 days with immediate improvement of his symptoms, including a notable increase in appetite over the next few days.
Within the neutrophils are purple organisms distinct from the nuclei identified as morulae. PCR testing for Anaplasma confirmed the result.
Anaplasmosis is a disease caused by the bacterium Anaplasma phagocytophilum, previously known as Ehrlichia phagocytophilum causing human granulocytic ehrlichiosis (HGE). A taxonomic change in 2001 identified that this organism belonged to the genus Anaplasma, and resulted in a change in the name of the disease to Anaplasmosis (1). These bacteria are obligate intracellular organisms in the Rickettsia family (1,2). Anaplasma cannot survive outside the cell and once it has been released, it rapidly induces uptake signals in other host cells (3). The number of Anaplasmosis cases reported to CDC has increased steadily since the disease became reportable, from 348 cases in 2000, to 5,762 in 2017(1).
Anaplasmosis is spread to people by tick bites primarily from the blacklegged tick (Ixodes scapularis) and the western black legged tick (Ixodes pacificus)(1,2). Anaplasmosis can be transmitted through blood transfusion and has been found in refrigerated blood more than a week after collection. Transfusion related infections have occurred from asymptomatic donors (1).
Signs and symptoms of Anaplasmosis typically begin within 1–2 weeks after the bite of an infected tick, which can be painless and often goes unnoticed. Early signs and symptoms (days 1-5) are usually mild or moderate and may include fever, chills, headache, muscle ache, nausea, vomiting, and lack of appetite (1,3). Rarely, if treatment is delayed or if there are other medical conditions present, Anaplasmosis can cause severe illness. Signs and symptoms of severe (late stage) illness can include respiratory failure, bleeding problems, organ failure, and death. Laboratory findings can include mild anemia, thrombocytopenia, leukopenia (characterized by relative and absolute lymphopenia and a left shift) and mild to moderate elevations in hepatic transaminases (1). Abnormal laboratory findings can appear in the first week of illness; however, normal laboratory findings do not rule out possible infection.
Co-infection with other tick borne illnesses such as Borrelia burgdorferi (Lyme disease), Babesia microti (Babesiosis), Ehrlichia muris eauclairensis (Erlichiosis), and Powassan virus can be seen so additional testing may be necessary in some patients. Methods for diagnosing Anaplasmosis include serology, molecular methods, and morphological identification. Though morphologic identification is extremely specific is lacks sensitivity making molecular methods such as PCR the diagnostic methods of choice (2). Treatment for most Rickettsial illnesses including Anaplasmosis are tetracyclines, especially doxycycline which is the drug of choice (1,3).
- Centers for Disease Control and Prevention: Anaplasmosis. https://www.cdc.gov/anaplasmosis/index.html
- Procop, Gary W., et al. Konemans Color Atlas and Textbook of Diagnostic Microbiology. 7th ed., Wolters Kluwer Health, 2017.
- Tille, Patricia M. Bailey & Scotts Diagnostic Microbiology. 13th ed., Elsevier, 2014.
-Casey Rankins, DO, is a 3rd year Anatomic and Clinical Pathology resident at the University of Vermont Medical Center.
-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.
Giorgis Okubazgi, an ASCP certified histotechnologist living and working in Ethiopia, and colleagues have published a brief editorial this month in AJCP detailing the current state of histopathology in Ethiopia: https://academic.oup.com/ajcp/article/doi/10.1093/ajcp/aqz144/5581862/. This type of cross-sectional survey of pathology infrastructure is crucial to understanding the gaps that exist in the current service provision models and where resources need to be focused to improve patient care and outcomes. If we just consider the incidence and prevalence of cancer in Ethiopia in a given year, we can start to grasp the magnitude of the problem. It is not fair or just to talk about the “current volume” of any of the 13 pathology laboratories Okubazgi et al reviewed because we can assume (and rightly so based on dozens of other observations in African countries) that, whatever the current volume of these laboratories, it is only a fraction of the population need for services. Consider the 2018 IARC data for Ethiopia, which estimates 67,573 new cancers for Ethiopia per year with 47,954 deaths (71% mortality). Comparing this directly with the US where 1,762,450 new cancers are expected in 2019 with 606,880 deaths (34% mortality), we can see immediately that the mortality differences is horrendous (and must be dealt with immediately) but that the relative rates of cancer seem to be skewed (why so many more cancers in the US?). These numbers for the US work out to about ~5400 cancers per year per 1,000,000 people in the US. Subtracting out skin cancers in Caucasians, assuming Ethiopia will economically improve its healthcare system overtime such that patient access increases, and shooting for a 50% malignant/benign ratio in surgical pathology biopsies of suspect lesions, we can estimate that the total country volume for suspected cancer tissue biopsies will eventually be between 131,146 and 2.5 million. Although that range seems quite vast, it at least provides us with figures to now understand the massive capacity challenges in Ethiopia. Considering there are 13 laboratories currently and equally dividing all that work among them, that would be 10,088 to 192,307 cases per lab per year. Another way to parse this would be by pathologists (again, assume a completely even distribution) for which there are currently 70 in country and 75 trainees. That would be 1873 to 35,714 cases per pathologist per year today or 904 to 17,241 cases per pathologists per year within the next 5 years. Keep in mind that this is JUST for suspected cancer biopsies and does not consider medical disease biopsies, asymptomatic screening tests (such as cervix or colon), obviously benign lesions, or products of conception evaluation. Considerations also have to be included for cytology samples which have been in practice in Ethiopia since 1965 and the role and volume of both forensic and medical autopsies. And, of course, as Okubazgi points out, 54% of these current labs serve only 20% of the population. So, what should surgical pathology services look like in Ethiopia going forward? Despite having three recognized major population concentrations, with a population of over 100 million, multiple populations of more than 1 million people are located in rural/non-urban settings. Only 6 of the current 13 laboratories are located in these areas and some 40 million people live in regions with no access to pathology. There are two solutions (not exclusive) to this type of access challenge which include 1) building additional laboratories and 2) created clear specimen referral networks. Several countries with much smaller populations such as Uganda and Rwanda have either built country-wide referral networks or increased the number of labs and pathologists/technicians to meet the current and projected population needs, respectively. Although neither of these countries has solved every challenge or optimized pathology services perfectly, they have instigated the programs and built value around these solutions which will lead to improved capacity and better patient care. However, for Ethiopia and its West African cousin, Nigeria, the distribution of citizens and size of the population will require a combined approach of both increased numbers of laboratories AND regional and/or national specimen referral networks. For both Nigeria and Ethiopia, there is a spectrum of wealth within the countries which means that robust public and private systems are needed in order to provide access to all citizens. With such a lack of capacity and resources currently in Ethiopia, the time is right for investment in Ethiopia through solid public programs with universal healthcare ideals, diversified private systems, and, most importantly, the opportunity to forge public-private partnerships as the system is being built up. As Paul Kagame has said, “In Africa today, we recognized trade and investment, and not aid, are pillars of development.” The gross domestic product (GDP) per capital in Ethiopia is currently $712; however, Ethiopia has one of the fastest growing economies in the world which means that disposable income and income spent on healthcare for a large cohort of citizens is expanding. By matching both internal and external investors in health, infrastructure, and technology with the sectors of the economy that are either under capacity or expected to grow, Ethiopia is ripe for solving its healthcare challenges, including access to diagnostics, through sustained economic development. This proposition is not without its challenges due to Ethiopia’s current restrictive policies on foreign investment as a non-collaborative endeavor. Despite this situation, there are channels and processes, most of which require local Ethiopian entrepreneurs and/or investing partners, through which powerful investments can be made for the betterment of health and society. It is at this moment when the healthcare infrastructure is under capacity but the economy is growing that Ethiopia needs investments in both public and private sector services so that the result on the far end of this economic boom is NOT a lack of access for the lowest incomed citizens. Nigeria’s boom in GDP and growth in economy happened nearly 30 years ago (with a relatively flat economy now) but those types of investments were not made such that now, the lowest incomed or impoverished citizens of Nigeria are left with essentially zero access to a global fee-for-service healthcare system. Let’s learn from the history of economies on the brink of transformation and not leave a single patient in Ethiopia without the chance for treatments and cure.
-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.