임상현장에서 말초혈액 도말검사(Peripheral Blood Smear, PB Smear)검사 소견을 묻는 의사 선생님들이 종종 있다. 사실 생소한 단어가 많아서 혈액내과나 소아혈액종양을 전공하신 선생님이 아니라면 학생 때 기억을 한참 되짚어야 할지도 모르겠다. 오늘은 PB smear report에서 자주 등장하는 용어와 임상적 의미에 대해 알아보겠다.
PB smear 검사에서 RBC 이상소견
Agglutination
RBC들이 뭉쳐있는 것을 의미하는 소견이다. 이것은 RBC의 표면이 항체로 뒤덮일때 생길 수 있는데, cold agglutinin이 존재하는 자가면역용혈빈혈 등에서 볼 수 있다.
Rouleaux formation
RBC가 동전쌓아놓은듯이 보이는 아주 유명한 소견으로, plasma cell myeloma (multiple myeloma)에서 보일 수 있다.
Anisocytosis
RBC 크기의 variability가 커져있다는 의미이다. CBC에서는 RDW수치가 증가한 것으로 나타난다. IDA나 megaloblastic anemia등과 관련된 소견이다.
Polychromasia
미성숙한 RBC가 pinkish blue-grey 색으로 보이는 것을 의미한다. 급성 출혈이나 용혈때 보일 수 있다.
Poikilocytosis
RBC의 모양이 정상과는 다르게 보인다는 것을 의미한다. PB smear report에서는 여러가지 단어로 RBC 모양이 표현되는데, 특정 모양의 poikilocytosis가 특정질환과 연관될 수도 있으나 nonspecific하게 나타나는 경우도 많다.
1. Tear drop cells
Dacrocyte라고도 하며, 적혈구의 한쪽 끝이 길게 꼬리처럼 나와있어 눈물방울처럼 보인다. PB smear에서 이것이 보인다면 bone marrow의 fibrosis를 시사하는 소견이다. Thalassemia나 다른 extramedullary hematopoiesis일때도 보일 수 있다.
2. Shistocytes
다른 말로 fragmented RBC라고도 하며, RBC가 혈관을 타고 순환하는 중에 기계적인 손상을 받았을 때 보인다. PB smear에서 이것이 보인다면 microangiopathic hemolytic anemia (MAHA)를 의심해야하며 대표적인 질환으로 TTP, HUS, DIC 등이 있을 수 있다.
3. Ovalocytes, elliptocytes
RBC의 장축이 단축의 2배 미만일 때는 ovalocytes이며, 장축이 단축의 2배이상 크면 elliptocytes이다. 이것이 hereditary elliptocytosis 등과 관련되어서 나타날 수 있으나 정상인에서도 10% 미만에서 관찰 될 수 있는 nonspecific한 소견이다.
4. Target cells
RBC가 과녁모양으로 동심원처럼 나타나는 소견으로, obstructive jaundice나 splenectomy 이후, hypochromic anemia에서 나타날 수 있다.
5. Sickle cells
겸상적혈구(sickle cell, drepanocyte)는 낫 모양으로 보이는 적혈구로서 sickle cell disease에서 특징적으로 나타난다.
6. Acanthocytes
가시적혈구(acanthocytes)는 불규칙적으로 가시가 돋은 모양을 하고 있는 적혈구이다. 인지질대사의 이상이나 적혈구막단백의 유전적인 결함과 연관되어있으며 splenectomy후에 보일 수 있다.
7. Stomatocytes
Slit모양의 central pallor가 보이는 소견이다. 말초혈액을 도말하는과정의 artifact로 나타날 수 있으며, hereditary sotmatocytosis 등과 연관되어 나타날 수 있다.
Basophilic stippling
RBC에 blue granule들이 보이는 것으로, ribosome이 비정상적으로 뭉쳐있는 것이다. RBC의 과도한 생성, 납중독, severe anemia, megaloblastic anemia 등과 관련이 있다.
Howell-Jolly bodies
RBC에 basophilic inclusion이 한 개 보이는 것이다. 이것은 DNA의 조각이 보이는 것이다. post-splenectomy state, megaloblastic anemia, hemolytic anemia와 관련이 있다.
Pappenheimer bodies
Ferritin aggregate가 RBC에 존재하는 것으로 철 과부하 혹은 비장기능저하증에서 발견된다.
Nucleated red blood cell (nRBC)
nRBC는 RBC precursor이다. 원래는 골수에 존재하며, 성숙 과정을 거쳐 적혈구가 될 세포가 말초혈액으로 나온것이다. PB smear에서 nRBC가 보이는 것은, 골수에서 증가된 RBC의 수요에 대응하기 위해 미성숙한 적혈구가 나온 것으로 이해하면 될 것이다. 혹은 골수가 백혈병 세포 등으로 꽉 찬 상태여서 밀려서 나왔을 수도 있다.
지금까지 PB Smear에서 나타날 수 있는 적혈구 이상 소견에 대해 알아 보았다. 이번에는 WBC 이상 소견에 대해 알아보겠다.
White Blood Cell (WBC, 백혈구)의 정상 소견
PB Smear에서 관찰되는 WBC 이상 소견에 대해 알아보기 위해서는 먼저 정상 소견을 알아야한다.
정상적으로는 말초 혈액에서는 neutrophil, monocyte, eosinophil, basophil, lymphocyte가 관찰될 수 있다. 이들이 참고 범위 이내로 관찰되는 것이 정상이고, 각각의 세포가 참고 범위를 벗어나 증가하거나 감소하게 되면 이상 소견으로 볼 수 있다.
Neutrophil (호중구)은 segmented neutrophil과 band neutrophil로 나뉘는데, segmented neutrophil은 크로마틴 끈으로 연결된 2~5개의 분엽을 갖고 있으며, band neutrophil은 U자 형태로 분엽이 되지 않은 세포를 말한다. 두 세포 모두 말초혈액도말 (PB Smear)에서 나타날 수 있으며 성인의 참고 범위는 segmented neutrophil이 50-70%, band neutrophil이 0-5%이다.
Monocyte (단구)는 청회색의 세포질을 가지며, 적혈구 크기의 2~3배 정도로 말초혈액의 정상혈구 중 가장 큰 것이 특징이다. 정상 성인에서는 백혈구의 약 4%를 차지한다.
Eosinophil(호산구)은 특징적으로 붉은 오렌지색의 굵은 과립이 세포질에 존재하여 호산성 염색성을 띤다. 백혈구의 약 3%정도를 차지하는 것이 정상적인 수치이다.
Basophil(호염기구)은 세포질 내에 호염기성 염색성을 보이는 진한 자주색의 과립이 핵을 덮고 있어 핵이 잘 보이지 않는 것이 특징적이다. 총 백혈구의 0.5%이내로 보이는 것이 정상이다.
Lymphocyte(림프구)는 크기가 다양하지만 small lymphocyte는 적혈구 크기와 같거나 약간 크다. 염색질이 짙으며 진한 청색을 띈다. Large lymphocyte는 크기가 더 크고, 세포질이 풍부하며 light sky blue색을 띤다. 림프구는 정상 성인에서 백혈구 수의 평균 34%정도를 차지한다.
Immature WBC (미성숙 백혈구) in PB Smear
이제부터는 미성숙한 백혈구가 말초혈액에 존재하거나 비정형 백혈구가 존재하는 등의 이상소견을 소개하겠다. 이를 이해하기 위해서는 먼저 neutrophil 계열 세포의 발달 단계를 알아야하는데, Myeloblast-Promyelocyte-Myelocyte-Metamyelocyte-Band neutrophil-Segmented neutrophil 순으로 발달이 진행된다.
Myeloblast (골수모세포)
Neutrophil을 만드는 세포의 발달단계는 myeloblast로부터 시작된다. Nucleoli가 1개 이상 존재하기도 하며, 높은 N/C ratio를 가진다. 골수에는 정상적으로 존재하지만, 이것이 말초혈액에서 관찰된다면 acute myeloid leukemia (AML)을 시사하는 소견이다.
Promyelocyte (전골수세포)
Myeloblast가 성숙하면 promyelocyte가 되는데 myeloblast보다 크기가 더 크며, primary granule이 세포질에서 특징적으로 관찰되어 basophilic하게 나타난다. Acute promyelocytic leukemia (AML M3)때 abnormal promyelocyte가 말초 혈액에서 관찰될 수 있다.
Auer rods와 Faggot cells
Auer rod는 myeloblast나 promyelocyte 등의 세포질에 존재하는 바늘모양의 red/pink color의 구조물이다. Primary granule 생성 과정에 이상이 생겨 나타난다. Auer rod가 세포질 안에 마치 캠프 파이어 할 때의 장작모양처럼 모여있는 세포를 faggot cell이라 부른다. Acute promyelocytic leukemia(APL, AML M3)에서 특징적으로 보이는 세포이다.
Myelocyte (골수세포)
Promyelocyte 다음 발달 단계이다. 핵은 promyelocyte보다 더 응축되어 있으며, primary granule과 secondary granule이 둘 다 존재하여 basophilic~cream색을 나타낸다. 이것이 말초 혈액에 존재한다면 left shift 혹은 shift to the left phenomenon이라고 PB smear report에 기록하는데, 세균 감염이 있을 경우에 나타날 수 있다.
Metamyelocyte (후골수세포)
Myelocyte 다음 발달 단계이다. 특징적으로 핵이 indented되어 있는데 이것은 50% 미만이다. 50% 이상 indented되어 있을 경우 다음 발달 단계인 band neutrophil로 분류한다. Myelocyte와 마찬가지로 metamyelocyte가 말초혈액에서 관찰될 경우 left shift, shift to the left phenomenon로 기록한다.
Leukoerythroblastic reaction
앞선 포스팅 말초혈액도말검사 (PB smear) 완벽정리 – RBC 소견에서 소개한 nRBC(nucleated red blood cell)가 myelocyte, metamyelocyte 등의 미성숙 백혈구와 함께 존재할 경우에는 leukoerythroblastic reaction이라고 PBS 소견에 기록한다. 이것은 골수에 space occupying lesion이 존재할 수 있음을 시사하는데, myelofibrosis, metastatic carcinoma, leukemia, multiple myeloma, Gaucher disease 등이 있을 수 있다. 또한 이외에도 trauma, sepsis, massive hemolysis 등의 상황에서도 나타날 수 있다.
Reactive lymphocytes
활성화된 림프구로서, 감염이나 염증반응에 대한 반응, 또는 leukemia나 lymphoma의 자극에 대한 반응으로서 보일 수 있으며, reactive lymphocyte는 malignant보다는 benign에 해당하는 표현이다.
Atypical lymphocytes
Reactive lymphocyte보다 좀 더 blast나 lymphoma 등의 tumor cell에 가까운 모양을 하고 있는 경우, 그렇지만 확실하게 AML이나 lymphoma 등의 증거가 부족한 경우에는 PB smear report에 atypical lymphocyte가 보인다는 표현으로 나가게 된다.
Plasma cell
골수에는 정상적으로 존재하는 항체를 생산하는 세포이다. 그렇지만, 말초혈액에서 plasma cell이 관찰된다면 plasma cell myeloma (multiple myeloma)를 강력히 시사하는 소견이다.
지금까지 정상 백혈구 (WBC) 와 미성숙 백혈구, 비정형 백혈구 등에 대하여 알아보았다.
다음에는 다른 백혈구 이상 소견들에 대해 알아보도록 하겠다.
WBC (백혈구)의 PB smear 비정상 소견
Hypersegmented neutrophil
앞서 정상 segmented neutrophil은 2~5개의 핵 분엽(lobe)을 갖는다고 했는데, 5개 이상의 분엽을 갖는 호중구가 5%이상이거나, 6개 이상의 분엽을 갖는 호중구가 하나 이상 관찰되는 경우에 해당한다. Megaloblastic anemia나 chronic infection, MDS와 연관이 있다. Methotrexate, hydroxyurea 등 세포 독성이 있는 치료를 받는 환자에서도 볼 수 있다.
Toxic granule (독성 과립)
Hypergranulation이라고도 하며, neutrophil의 세포질에 과립이 증가하여 염색이 진하게 된 상태이다. Infection과 inflammation 상황에서 나타날 수 있으며, G-CSF 치료 후에 나타날 수 있다.
Vacuolation
주로 neutrophil과 monocyte의 세포질에 염색이 되지 않는 부분(vacuole)이다. Toxic granule과 함께 존재할 경우 대개 중증 패혈증을 시사하는 소견일 수 있지만, 두 시간 이상 방치한 혈액으로 말초혈액 도말 표본을 만들면 인공적으로 생길 수도 있다. 세균감염, 진균감염, 화상, 항암치료 후에도 나타날 수 있다.
Hypogranulation
Neutrophil의 granulation이 감소하거나 존재하지 않는 상태이다. MDS, MPN, infection과 연관이 있다.
Hyposegmented neutrophil
호중구의 핵분엽의 발달이 정지된 상태로 위 사진과 같이 쌍안경을 쓰고 있는 모양으로 보인다. 상염색체 우성 유전 질환인 Pelger-Huët anomaly에서 보일 수 있으며, MDS, CML, AML 등에서도 이와 유사한 형태가 나타나서pseudo-Pelger-Huët anomaly라고 부른다.
Döhle body
Neutrophil 세포질의 가장자리에 위치하는 gray-blue 색을 띠는 구조물이다. 단독으로 나타날 수도 있고 여러 개가 보일 수도 있다. Nonspecific reactive change로서, 감염, 화상, 항암 요법, G-CSF 치료 등과 연관되어 나타날 수 있다.
Smudge cell, basket cell
깨진 백혈구를 의미하는 것으로 잘 부서지는 세포가 증가한 것을 시사하는 소견이다. 이것이 증가할 때는 CLL, ALL, atypical lymphocytosis를 의심해 보아야한다.
Platelet (혈소판) 소견
EDTA-induced pseudothrombocytopenia
임상에서 혈소판 수치가 떨어져 있을 경우에, 진짜로 혈소판 수치가 떨어져 있는지 여부를 알아보기 위해서 PB smear 검사를 내는 경우가 있다. 만약 현미경 검경시에 이렇게 platelet aggregation이 관찰된다면 sodium citrate 튜브에 채혈하여 혈소판 수를 다시 측정해야 한다. 배율을 x1000로 맞춘 상태에서 10시야를 관찰 한 후 이때 나타난 평균적인 혈소판 수에 20,000을 곱하면 평균 혈소판수를 계산할 수 있다.
Hypogranular Platelets
혈소판이 희미하게 보이는 경우이다. MDS나 MPN의 경우를 시사하는 소견일 수 있으나, megakaryocyte 이외의 다른 세포에서 떨어진 조각이 이렇게 보일 수도 있다.
사진을 보니 예전에 배웠던 기억이 새록새록하네요 포스팅 감사합니다
임상에 계신 선생님들이 PBS소견을 해석할때 도움이 되었으면 좋겠네요 🙂
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