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The Pathologist / Issues / 2022 / Feb / Case of the Month
Histology Histology Microscopy and imaging

Case of the Month

02/21/2022 Quick Read (pre 2022) 1 min read

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A 43-year-old man presented with a puncture injury on the volar surface of the right index fingertip. On examination, there was profuse swelling of the fingertip with dusky skin changes. During operative exploration of the wound, the injury extended down to the flexor tendon sheath (Figure 1A). On further revision, the fingertip was amputated at the distal phalanx (Figure 1B,C). Microscopic examination is shown in in Figure 2.

Figure 1. A) Initial surgical wound following the first debridement surgery; note the contrast between the injection site and the area of debridement. B,C) Amputated fingertip following subsequent surgical revision; note the dusky necrotic appearance of the fingertip.

What is most likely represented in the microscopic images?

a. Ochronotic bodies
b. Tattoo pigmentation
c. Grease​​​​​​​
d. Pigment incontinence

Click here to register your guess.​​​​​​​

Do you have an interesting case that you would like us to feature? Email it to edit@thepathologist.com.

Answer to January/February’s Case of the Month

C. Sickle beta-plus thalassemia (Hb Sβ+ thalassemia)

Infants from high-risk ethnic groups are strongly recommended neonatal screening for sickle cell disease because early diagnosis and comprehensive care can markedly reduce morbidity and mortality in early childhood. To make an accurate interpretation, it’s important to recognize the different hemoglobin electrophoresis patterns in newborns by placing hemoglobin A, F, S, and other variants in order of relative abundance. Healthy infants have far more hemoglobin F than A, so the normal pattern is FA. Hb F gradually wanes during infancy and most reach adult levels at six to 12 months of age. In newborns with sickle cell disorders, hemoglobin F is also most abundant. Sickle cell trait (Hb AS) manifests as FAS, which means more hemoglobin A than S is produced. Both sickle cell anemia (Hb SS) and sickle beta-zero thalassemia (Hb Sβ0 thalassemia) cannot produce hemoglobin A; as a result, both manifest the FS pattern.

This newborn’s hemoglobin electrophoresis pattern is FSA, which indicates the coexistence of sickle cell trait and beta-plus trait (Hb Sβ+ thalassemia), leading to more production of hemoglobin S than A. Hemoglobin A2 is undetectable or produced at very low levels in newborns, so a lack of elevated Hb A2 is a common finding in beta thalassemia trait. Because of the dominance of hemoglobin F, hemoglobin A can also be insufficient for detection at birth. In other words, sickle beta-plus thalassemia may manifest as FS pattern (as seen in SS, sickle beta-zero thalassemia, or sickle with hereditary persistence of hemoglobin F). If the pattern is FS, it’s important to repeat testing in few months or perform molecular studies to make a definitive diagnosis. 

This young patient had no clinical follow-up for two years. At 32 months, he presented to the children’s emergency room with acute chest pain and shortness of breath. CT scan confirmed bilateral pulmonary embolism; the patient responded well to anticoagulant therapy. Upon hospital admission, his RBC indices and hemoglobin electrophoresis pattern demonstrated classic findings seen with sickle beta thalassemia trait: significant microcytic anemia, hemoglobin S>50%, elevated hemoglobin A2 (>3.5%), and normal or slightly elevated hemoglobin F.

Submitted by Ping Sun, Assistant Professor of Pathology, and Daniel Marko, Assistant Professor of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.

Further Reading

  1. E Vichinsky et al., “Newborn screening for sickle cell disease: effect on mortality,” Pediatrics, 81, 749 (1988). PMID: 3368274.
  2. BJ Bain et al., “Investigation of Variant Haemoglobins and Thalassaemias,” Practical Haematology. Elsevier Health Sciences: 2016.
  3. ​​​​​​​J Michlitsch et al., “Newborn screening for hemoglobinopathies in California,” Pediatr Blood Cancer, 52, 486 (2009). PMID: 19061217.

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